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Urasaki, Yasuyo, and Thuc T. Le. "Differentiation of Essential Oils Using Nanofluidic Protein Post-Translational Modification Profiling." Molecules 24, no. 13 (June 27, 2019): 2383. http://dx.doi.org/10.3390/molecules24132383.
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Current methods for the authentication of essential oils focus on analyzing their chemical composition. This study describes the use of nanofluidic protein post-translational modification (PTM) profiling to differentiate essential oils by analyzing their biochemical effects. Protein PTM profiling was used to measure the effects of four essential oils, copaiba, mandarin, Melissa, and turmeric, on the phosphorylation of MEK1, MEK2, and ERK1/2 in the MAPK signaling pathway; Akt and 4EBP1 in the pI3K/Akt/mTOR signaling pathway; and STAT3 in the JAK/STAT signaling pathway in cultured HepG2 cells. The gain or loss of the phosphorylation of these proteins served as direct read-outs for the positive or negative regulatory effects of essential oils on their respective signaling pathways. Furthermore, protein PTM profiling and GC-MS were employed side-by-side to assess the quality of the essential oils. In general, protein PTM profiling data concurred with GC-MS data on the identification of adulterated mandarin, Melissa, and turmeric essential oils. Most interestingly, protein PTM profiling data identified the differences in biochemical effects between copaiba essential oils, which were indistinguishable with GC-MS data on their chemical composition. Taken together, nanofluidic protein PTM profiling represents a robust method for the assessment of the quality and therapeutic potential of essential oils.
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Wang, Duolin, Yanchun Liang, and Dong Xu. "Capsule network for protein post-translational modification site prediction." Bioinformatics 35, no. 14 (December 6, 2018): 2386–94. http://dx.doi.org/10.1093/bioinformatics/bty977.
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Abstract Motivation Computational methods for protein post-translational modification (PTM) site prediction provide a useful approach for studying protein functions. The prediction accuracy of the existing methods has significant room for improvement. A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data. Results We proposed a CapsNet for predicting protein PTM sites, including phosphorylation, N-linked glycosylation, N6-acetyllysine, methyl-arginine, S-palmitoyl-cysteine, pyrrolidone-carboxylic-acid and SUMOylation sites. The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data. The capsule length also gives an accurate estimate for the confidence of the PTM prediction. We further demonstrated that the internal capsule features could be trained as a motif detector of phosphorylation sites when no kinase-specific phosphorylation labels were provided. In addition, CapsNet generates robust representations that have strong discriminant power in distinguishing kinase substrates from different kinase families. Our study sheds some light on the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems. Availability and implementation The codes are free to download from https://github.com/duolinwang/CapsNet_PTM. Supplementary information Supplementary data are available at Bioinformatics online.
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Hernandez-Valladares, Maria, Rebecca Wangen, Frode S. Berven, and Astrid Guldbrandsen. "Protein Post-Translational Modification Crosstalk in Acute Myeloid Leukemia Calls for Action." Current Medicinal Chemistry 26, no. 28 (October 25, 2019): 5317–37. http://dx.doi.org/10.2174/0929867326666190503164004.
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Background: Post-translational modification (PTM) crosstalk is a young research field. However, there is now evidence of the extraordinary characterization of the different proteoforms and their interactions in a biological environment that PTM crosstalk studies can describe. Besides gene expression and phosphorylation profiling of acute myeloid leukemia (AML) samples, the functional combination of several PTMs that might contribute to a better understanding of the complexity of the AML proteome remains to be discovered. Objective: By reviewing current workflows for the simultaneous enrichment of several PTMs and bioinformatics tools to analyze mass spectrometry (MS)-based data, our major objective is to introduce the PTM crosstalk field to the AML research community. Results: After an introduction to PTMs and PTM crosstalk, this review introduces several protocols for the simultaneous enrichment of PTMs. Two of them allow a simultaneous enrichment of at least three PTMs when using 0.5-2 mg of cell lysate. We have reviewed many of the bioinformatics tools used for PTM crosstalk discovery as its complex data analysis, mainly generated from MS, becomes challenging for most AML researchers. We have presented several non-AML PTM crosstalk studies throughout the review in order to show how important the characterization of PTM crosstalk becomes for the selection of disease biomarkers and therapeutic targets. Conclusion: Herein, we have reviewed the advances and pitfalls of the emerging PTM crosstalk field and its potential contribution to unravel the heterogeneity of AML. The complexity of sample preparation and bioinformatics workflows demands a good interaction between experts of several areas.
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Pascovici, Dana, Jemma X. Wu, Matthew J. McKay, Chitra Joseph, Zainab Noor, Karthik Kamath, Yunqi Wu, Shoba Ranganathan, Vivek Gupta, and Mehdi Mirzaei. "Clinically Relevant Post-Translational Modification Analyses—Maturing Workflows and Bioinformatics Tools." International Journal of Molecular Sciences 20, no. 1 (December 20, 2018): 16. http://dx.doi.org/10.3390/ijms20010016.
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Post-translational modifications (PTMs) can occur soon after translation or at any stage in the lifecycle of a given protein, and they may help regulate protein folding, stability, cellular localisation, activity, or the interactions proteins have with other proteins or biomolecular species. PTMs are crucial to our functional understanding of biology, and new quantitative mass spectrometry (MS) and bioinformatics workflows are maturing both in labelled multiplexed and label-free techniques, offering increasing coverage and new opportunities to study human health and disease. Techniques such as Data Independent Acquisition (DIA) are emerging as promising approaches due to their re-mining capability. Many bioinformatics tools have been developed to support the analysis of PTMs by mass spectrometry, from prediction and identifying PTM site assignment, open searches enabling better mining of unassigned mass spectra—many of which likely harbour PTMs—through to understanding PTM associations and interactions. The remaining challenge lies in extracting functional information from clinically relevant PTM studies. This review focuses on canvassing the options and progress of PTM analysis for large quantitative studies, from choosing the platform, through to data analysis, with an emphasis on clinically relevant samples such as plasma and other body fluids, and well-established tools and options for data interpretation.
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Dunphy, Katie, Paul Dowling, Despina Bazou, and Peter O’Gorman. "Current Methods of Post-Translational Modification Analysis and Their Applications in Blood Cancers." Cancers 13, no. 8 (April 16, 2021): 1930. http://dx.doi.org/10.3390/cancers13081930.
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Post-translational modifications (PTMs) add a layer of complexity to the proteome through the addition of biochemical moieties to specific residues of proteins, altering their structure, function and/or localization. Mass spectrometry (MS)-based techniques are at the forefront of PTM analysis due to their ability to detect large numbers of modified proteins with a high level of sensitivity and specificity. The low stoichiometry of modified peptides means fractionation and enrichment techniques are often performed prior to MS to improve detection yields. Immuno-based techniques remain popular, with improvements in the quality of commercially available modification-specific antibodies facilitating the detection of modified proteins with high affinity. PTM-focused studies on blood cancers have provided information on altered cellular processes, including cell signaling, apoptosis and transcriptional regulation, that contribute to the malignant phenotype. Furthermore, the mechanism of action of many blood cancer therapies, such as kinase inhibitors, involves inhibiting or modulating protein modifications. Continued optimization of protocols and techniques for PTM analysis in blood cancer will undoubtedly lead to novel insights into mechanisms of malignant transformation, proliferation, and survival, in addition to the identification of novel biomarkers and therapeutic targets. This review discusses techniques used for PTM analysis and their applications in blood cancer research.
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Wang, BingHua, Minghui Wang, and Ao Li. "Prediction of post-translational modification sites using multiple kernel support vector machine." PeerJ 5 (April 27, 2017): e3261. http://dx.doi.org/10.7717/peerj.3261.
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Protein post-translational modification (PTM) is an important mechanism that is involved in the regulation of protein function. Considering the high-cost and labor-intensive of experimental identification, many computational prediction methods are currently available for the prediction of PTM sites by using protein local sequence information in the context of conserved motif. Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. To largely make use of local sequence information and site-modification relationships, we developed a local sequence kernel and Gaussian interaction profile kernel, respectively. Multiple kernels were further combined to train SVM for efficiently leveraging kernel information to boost predictive performance. We compared the proposed method with existing PTM prediction methods. The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction.
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Chen, Zhen, Xuhan Liu, Fuyi Li, Chen Li, Tatiana Marquez-Lago, André Leier, Tatsuya Akutsu, et al. "Large-scale comparative assessment of computational predictors for lysine post-translational modification sites." Briefings in Bioinformatics 20, no. 6 (October 4, 2018): 2267–90. http://dx.doi.org/10.1093/bib/bby089.
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Abstract Lysine post-translational modifications (PTMs) play a crucial role in regulating diverse functions and biological processes of proteins. However, because of the large volumes of sequencing data generated from genome-sequencing projects, systematic identification of different types of lysine PTM substrates and PTM sites in the entire proteome remains a major challenge. In recent years, a number of computational methods for lysine PTM identification have been developed. These methods show high diversity in their core algorithms, features extracted and feature selection techniques and evaluation strategies. There is therefore an urgent need to revisit these methods and summarize their methodologies, to improve and further develop computational techniques to identify and characterize lysine PTMs from the large amounts of sequence data. With this goal in mind, we first provide a comprehensive survey on a large collection of 49 state-of-the-art approaches for lysine PTM prediction. We cover a variety of important aspects that are crucial for the development of successful predictors, including operating algorithms, sequence and structural features, feature selection, model performance evaluation and software utility. We further provide our thoughts on potential strategies to improve the model performance. Second, in order to examine the feasibility of using deep learning for lysine PTM prediction, we propose a novel computational framework, termed MUscADEL (Multiple Scalable Accurate Deep Learner for lysine PTMs), using deep, bidirectional, long short-term memory recurrent neural networks for accurate and systematic mapping of eight major types of lysine PTMs in the human and mouse proteomes. Extensive benchmarking tests show that MUscADEL outperforms current methods for lysine PTM characterization, demonstrating the potential and power of deep learning techniques in protein PTM prediction. The web server of MUscADEL, together with all the data sets assembled in this study, is freely available at http://muscadel.erc.monash.edu/. We anticipate this comprehensive review and the application of deep learning will provide practical guide and useful insights into PTM prediction and inspire future bioinformatics studies in the related fields.
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Yang, Tangpo, Zheng Liu, and Xiang David Li. "Developing diazirine-based chemical probes to identify histone modification ‘readers’ and ‘erasers’." Chemical Science 6, no. 2 (2015): 1011–17. http://dx.doi.org/10.1039/c4sc02328e.
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Malik, Arshi, Sarah Afaq, Afaf S. Alwabli, and Khalid Al-ghmady. "Networking of predicted post-translational modification (PTM) sites in human EGFR." Bioinformation 15, no. 7 (July 31, 2019): 448–54. http://dx.doi.org/10.6026/97320630015448.
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Arntzen, Magnus Ø., Christoffer Leif Osland, Christopher Rasch-Olsen Raa, Reidun Kopperud, Stein-Ove Døskeland, Aurélia E. Lewis, and Clive S. D'Santos. "POSTMan (POST-translational modification analysis), a software application for PTM discovery." PROTEOMICS 9, no. 5 (March 2009): 1400–1406. http://dx.doi.org/10.1002/pmic.200800500.
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Duong, Van-An, Onyou Nam, EonSeon Jin, Jong-Moon Park, and Hookeun Lee. "Discovery of Post-Translational Modifications in Emiliania huxleyi." Molecules 26, no. 7 (April 2, 2021): 2027. http://dx.doi.org/10.3390/molecules26072027.
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Emiliania huxleyi is a cosmopolitan coccolithophore that plays an essential role in global carbon and sulfur cycling, and contributes to marine cloud formation and climate regulation. Previously, the proteomic profile of Emiliania huxleyi was investigated using a three-dimensional separation strategy combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The current study reuses the MS/MS spectra obtained, for the global discovery of post-translational modifications (PTMs) in this species without specific enrichment methods. Twenty-five different PTM types were examined using Trans-Proteomic Pipeline (Comet and PeptideProphet). Overall, 13,483 PTMs were identified in 7421 proteins. Methylation was the most frequent PTM with more than 2800 modified sites, and lysine was the most frequently modified amino acid with more than 4000 PTMs. The number of proteins identified increased by 22.5% to 18,780 after performing the PTM search. Compared to intact peptides, the intensities of some modified peptides were superior or equivalent. The intensities of some proteins increased dramatically after the PTM search. Gene ontology analysis revealed that protein persulfidation was related to photosynthesis in Emiliania huxleyi. Additionally, various membrane proteins were found to be phosphorylated. Thus, our global PTM discovery platform provides an overview of PTMs in the species and prompts further studies to uncover their biological functions. The combination of a three-dimensional separation method with global PTM search is a promising approach for the identification and discovery of PTMs in other species.
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Wang, Duolin, Dongpeng Liu, Jiakang Yuchi, Fei He, Yuexu Jiang, Siteng Cai, Jingyi Li, and Dong Xu. "MusiteDeep: a deep-learning based webserver for protein post-translational modification site prediction and visualization." Nucleic Acids Research 48, W1 (April 23, 2020): W140—W146. http://dx.doi.org/10.1093/nar/gkaa275.
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Abstract MusiteDeep is an online resource providing a deep-learning framework for protein post-translational modification (PTM) site prediction and visualization. The predictor only uses protein sequences as input and no complex features are needed, which results in a real-time prediction for a large number of proteins. It takes less than three minutes to predict for 1000 sequences per PTM type. The output is presented at the amino acid level for the user-selected PTM types. The framework has been benchmarked and has demonstrated competitive performance in PTM site predictions by other researchers. In this webserver, we updated the previous framework by utilizing more advanced ensemble techniques, and providing prediction and visualization for multiple PTMs simultaneously for users to analyze potential PTM cross-talks directly. Besides prediction, users can interactively review the predicted PTM sites in the context of known PTM annotations and protein 3D structures through homology-based search. In addition, the server maintains a local database providing pre-processed PTM annotations from Uniport/Swiss-Prot for users to download. This database will be updated every three months. The MusiteDeep server is available at https://www.musite.net. The stand-alone tools for locally using MusiteDeep are available at https://github.com/duolinwang/MusiteDeep_web.
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Xu, Yongjie, Wei Wu, Qiu Han, Yaling Wang, Cencen Li, Pengpeng Zhang, and Haixia Xu. "Post-translational modification control of RNA-binding protein hnRNPK function." Open Biology 9, no. 3 (March 2019): 180239. http://dx.doi.org/10.1098/rsob.180239.
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Heterogeneous nuclear ribonucleoprotein K (hnRNPK), a ubiquitously occurring RNA-binding protein (RBP), can interact with numerous nucleic acids and various proteins and is involved in a number of cellular functions including transcription, translation, splicing, chromatin remodelling, etc. Through its abundant biological functions, hnRNPK has been implicated in cellular events including proliferation, differentiation, apoptosis, DNA damage repair and the stress and immune responses. Thus, it is critical to understand the mechanism of hnRNPK regulation and its downstream effects on cancer and other diseases. A number of recent studies have highlighted that several post-translational modifications (PTMs) possibly play an important role in modulating hnRNPK function. Phosphorylation is the most widely occurring PTM in hnRNPK. For example, in vivo analyses of sites such as S116 and S284 illustrate the purpose of PTM of hnRNPK in altering its subcellular localization and its ability to bind target nucleic acids or proteins. Other PTMs such as methylation, ubiquitination, sumoylation, glycosylation and proteolytic cleavage are increasingly implicated in the regulation of DNA repair, cellular stresses and tumour growth. In this review, we describe the PTMs that impact upon hnRNPK function on gene expression programmes and different disease states. This knowledge is key in allowing us to better understand the mechanism of hnRNPK regulation.
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Holstein, Elisa, Annalena Dittmann, Anni Kääriäinen, Vilma Pesola, Jarkko Koivunen, Taina Pihlajaniemi, Alexandra Naba, and Valerio Izzi. "The Burden of Post-Translational Modification (PTM)—Disrupting Mutations in the Tumor Matrisome." Cancers 13, no. 5 (March 3, 2021): 1081. http://dx.doi.org/10.3390/cancers13051081.
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Background: To evaluate the occurrence of mutations affecting post-translational modification (PTM) sites in matrisome genes across different tumor types, in light of their genomic and functional contexts and in comparison with the rest of the genome. Methods: This study spans 9075 tumor samples and 32 tumor types from The Cancer Genome Atlas (TCGA) Pan-Cancer cohort and identifies 151,088 non-silent mutations in the coding regions of the matrisome, of which 1811 affecting known sites of hydroxylation, phosphorylation, N- and O-glycosylation, acetylation, ubiquitylation, sumoylation and methylation PTM. Results: PTM-disruptive mutations (PTMmut) in the matrisome are less frequent than in the rest of the genome, seem independent of cell-of-origin patterns but show dependence on the nature of the matrisome protein affected and the background PTM types it generally harbors. Also, matrisome PTMmut are often found among structural and functional protein regions and in proteins involved in homo- and heterotypic interactions, suggesting potential disruption of matrisome functions. Conclusions: Though quantitatively minoritarian in the spectrum of matrisome mutations, PTMmut show distinctive features and damaging potential which might concur to deregulated structural, functional, and signaling networks in the tumor microenvironment.
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Ito, K. "Impact of post-translational modifications of proteins on the inflammatory process." Biochemical Society Transactions 35, no. 2 (March 20, 2007): 281–83. http://dx.doi.org/10.1042/bst0350281.
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PTM (post-translational modification) is the chemical modification of a protein after its translation. The well-studied PTM is phosphorylation, but, recently, PTMs have been re-focused by extensive studies on histone modifications and the discovery of the ubiquitin system. Histone acetylation is the well-established epigenetic regulator for gene expression. Recent studies show that different patterns of PTMs and cross-talk of individual modifications (acetylation, methylation, phosphorylation) are keys of gene regulation (known as the ‘histone code’). As well as histone, non-histone proteins are also targets of acetylation. For instance, NF-κB (nuclear factor κB), a transcriptional factor, is regulated dynamically by acetylation/deacetylation. Acetylation of NF-κB [RelA (p65)] at Lys310 enhances its transcriptional activity, which is inhibited by SIRT1 deacetylase, type III HDAC (histone deacetylase). We also found that acetylated NF-κB preferentially bound to the IL-8 (interleukin 8) gene promoter, but not to GM-CSF (granulocyte/macrophage colony-stimulating factor), suggesting NF-κB acetylation is involved in selective gene induction as well as an increased level of transcription. A receptor of glucocorticoid, a potent anti-inflammatory agent, is also a target of acetylation. The glucocorticoid receptor is highly acetylated after ligand binding but its deacetylation is necessary for gene repression through binding to NF-κB. As well as acetylation, other PTMs, such as nitration, carbonylation and ubiquitination on transcriptional/nuclear factors, are taking part in the inflammatory process. Cross-talk of individual modifications on proteins deserves further evaluation in the future (as ‘protein code’).
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Dilweg, Ivar W., and Remus T. Dame. "Post-translational modification of nucleoid-associated proteins: an extra layer of functional modulation in bacteria?" Biochemical Society Transactions 46, no. 5 (October 4, 2018): 1381–92. http://dx.doi.org/10.1042/bst20180488.
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Post-translational modification (PTM) of histones has been investigated in eukaryotes for years, revealing its widespread occurrence and functional importance. Many PTMs affect chromatin folding and gene activity. Only recently the occurrence of such modifications has been recognized in bacteria. However, it is unclear whether PTM of the bacterial counterparts of eukaryotic histones, nucleoid-associated proteins (NAPs), bears a comparable significance. Here, we scrutinize proteome mass spectrometry data for PTMs of the four most abundantly present NAPs in Escherichia coli (H-NS, HU, IHF and FIS). This approach allowed us to identify a total of 101 unique PTMs in the 11 independent proteomic studies covered in this review. Combined with structural and genetic information on these proteins, we describe potential effects of these modifications (perturbed DNA-binding, structural integrity or interaction with other proteins) on their function.
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Tromp, Angelino T., Michiel Van Gent, Joris P. Jansen, Lisette M. Scheepmaker, Anneroos Velthuizen, Carla J. C. De Haas, Kok P. M. Van Kessel, et al. "Host–Receptor Post-Translational Modifications Refine Staphylococcal Leukocidin Cytotoxicity." Toxins 12, no. 2 (February 6, 2020): 106. http://dx.doi.org/10.3390/toxins12020106.
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Staphylococcal bi-component pore-forming toxins, also known as leukocidins, target and lyse human phagocytes in a receptor-dependent manner. S-components of the leukocidins Panton-Valentine leukocidin (PVL), γ-haemolysin AB (HlgAB) and CB (HlgCB), and leukocidin ED (LukED) specifically employ receptors that belong to the class of G-protein coupled receptors (GPCRs). Although these receptors share a common structural architecture, little is known about the conserved characteristics of the interaction between leukocidins and GPCRs. In this study, we investigated host cellular pathways contributing to susceptibility towards S. aureus leukocidin cytotoxicity. We performed a genome-wide CRISPR/Cas9 library screen for toxin-resistance in U937 cells sensitized to leukocidins by ectopic expression of different GPCRs. Our screen identifies post-translational modification (PTM) pathways involved in the sulfation and sialylation of the leukocidin-receptors. Subsequent validation experiments show differences in the impact of PTM moieties on leukocidin toxicity, highlighting an additional layer of refinement and divergence in the staphylococcal host-pathogen interface. Leukocidin receptors may serve as targets for anti-staphylococcal interventions and understanding toxin-receptor interactions will facilitate the development of innovative therapeutics. Variations in the genes encoding PTM pathways could provide insight into observed differences in susceptibility of humans to infections with S. aureus.
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Dougherty, Shannon E., Austin O. Maduka, Toshifumi Inada, and Gustavo M. Silva. "Expanding Role of Ubiquitin in Translational Control." International Journal of Molecular Sciences 21, no. 3 (February 9, 2020): 1151. http://dx.doi.org/10.3390/ijms21031151.
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The eukaryotic proteome has to be precisely regulated at multiple levels of gene expression, from transcription, translation, and degradation of RNA and protein to adjust to several cellular conditions. Particularly at the translational level, regulation is controlled by a variety of RNA binding proteins, translation and associated factors, numerous enzymes, and by post-translational modifications (PTM). Ubiquitination, a prominent PTM discovered as the signal for protein degradation, has newly emerged as a modulator of protein synthesis by controlling several processes in translation. Advances in proteomics and cryo-electron microscopy have identified ubiquitin modifications of several ribosomal proteins and provided numerous insights on how this modification affects ribosome structure and function. The variety of pathways and functions of translation controlled by ubiquitin are determined by the various enzymes involved in ubiquitin conjugation and removal, by the ubiquitin chain type used, by the target sites of ubiquitination, and by the physiologic signals triggering its accumulation. Current research is now elucidating multiple ubiquitin-mediated mechanisms of translational control, including ribosome biogenesis, ribosome degradation, ribosome-associated protein quality control (RQC), and redox control of translation by ubiquitin (RTU). This review discusses the central role of ubiquitin in modulating the dynamism of the cellular proteome and explores the molecular aspects responsible for the expanding puzzle of ubiquitin signals and functions in translation.
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Xue, Xiangfei, Xiao Zhang, Fenyong Sun, and Jiayi Wang. "Emerging Role of Protein Post-Translational Modification in the Potential Clinical Application of Cancer." Nano LIFE 10, no. 01n02 (March 2020): 2040008. http://dx.doi.org/10.1142/s1793984420400085.
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Cancer, one of the largest public health problems in the world, greatly endangers human health. Every country in the world faces a significant burden due to cancer. Protein post-translational modification (PTM) plays a very important role in life. PTM makes the structure of proteins more complex and the functions more perfect. Common PTM processes include methylation, acetylation, phosphorylation, glycosylation and ubiquitination. In this paper, we introduce several common types of PTMs that were discovered in recent years in various cancer types, especially the early stages of cancer, and we explore the role of related molecules in cancer screening, diagnosis, disease surveillance and prognosis. We look forward to using PTM-relevant molecules as markers for the early diagnosis of cancer, after further in-depth research and large-scale clinical trials, to contribute to the early and accurate diagnosis of cancer, thereby improving the prognosis.
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Kumar, Ramesh, Divya Mehta, Nimisha Mishra, Debasis Nayak, and Sujatha Sunil. "Role of Host-Mediated Post-Translational Modifications (PTMs) in RNA Virus Pathogenesis." International Journal of Molecular Sciences 22, no. 1 (December 30, 2020): 323. http://dx.doi.org/10.3390/ijms22010323.
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Being opportunistic intracellular pathogens, viruses are dependent on the host for their replication. They hijack host cellular machinery for their replication and survival by targeting crucial cellular physiological pathways, including transcription, translation, immune pathways, and apoptosis. Immediately after translation, the host and viral proteins undergo a process called post-translational modification (PTM). PTMs of proteins involves the attachment of small proteins, carbohydrates/lipids, or chemical groups to the proteins and are crucial for the proteins’ functioning. During viral infection, host proteins utilize PTMs to control the virus replication, using strategies like activating immune response pathways, inhibiting viral protein synthesis, and ultimately eliminating the virus from the host. PTM of viral proteins increases solubility, enhances antigenicity and virulence properties. However, RNA viruses are devoid of enzymes capable of introducing PTMs to their proteins. Hence, they utilize the host PTM machinery to promote their survival. Proteins from viruses belonging to the family: Togaviridae, Flaviviridae, Retroviridae, and Coronaviridae such as chikungunya, dengue, zika, HIV, and coronavirus are a few that are well-known to be modified. This review discusses various host and virus-mediated PTMs that play a role in the outcome during the infection.
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Wang, Qi, Keyun Wang, and Mingliang Ye. "Strategies for large-scale analysis of non-histone protein methylation by LC-MS/MS." Analyst 142, no. 19 (2017): 3536–48. http://dx.doi.org/10.1039/c7an00954b.
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Cheng, Alice, Charles E. Grant, William S. Noble, and Timothy L. Bailey. "MoMo: discovery of statistically significant post-translational modification motifs." Bioinformatics 35, no. 16 (December 31, 2018): 2774–82. http://dx.doi.org/10.1093/bioinformatics/bty1058.
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Abstract Motivation Post-translational modifications (PTMs) of proteins are associated with many significant biological functions and can be identified in high throughput using tandem mass spectrometry. Many PTMs are associated with short sequence patterns called ‘motifs’ that help localize the modifying enzyme. Accordingly, many algorithms have been designed to identify these motifs from mass spectrometry data. Accurate statistical confidence estimates for discovered motifs are critically important for proper interpretation and in the design of downstream experimental validation. Results We describe a method for assigning statistical confidence estimates to PTM motifs, and we demonstrate that this method provides accurate P-values on both simulated and real data. Our methods are implemented in MoMo, a software tool for discovering motifs among sets of PTMs that we make available as a web server and as downloadable source code. MoMo re-implements the two most widely used PTM motif discovery algorithms—motif-x and MoDL—while offering many enhancements. Relative to motif-x, MoMo offers improved statistical confidence estimates and more accurate calculation of motif scores. The MoMo web server offers more proteome databases, more input formats, larger inputs and longer running times than the motif-x web server. Finally, our study demonstrates that the confidence estimates produced by motif-x are inaccurate. This inaccuracy stems in part from the common practice of drawing ‘background’ peptides from an unshuffled proteome database. Our results thus suggest that many of the papers that use motif-x to find motifs may be reporting results that lack statistical support. Availability and implementation The MoMo web server and source code are provided at http://meme-suite.org. Supplementary information Supplementary data are available at Bioinformatics online.
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Taylor, Bethany C., and Nicolas L. Young. "Combinations of histone post-translational modifications." Biochemical Journal 478, no. 3 (February 10, 2021): 511–32. http://dx.doi.org/10.1042/bcj20200170.
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Histones are essential proteins that package the eukaryotic genome into its physiological state of nucleosomes, chromatin, and chromosomes. Post-translational modifications (PTMs) of histones are crucial to both the dynamic and persistent regulation of the genome. Histone PTMs store and convey complex signals about the state of the genome. This is often achieved by multiple variable PTM sites, occupied or unoccupied, on the same histone molecule or nucleosome functioning in concert. These mechanisms are supported by the structures of ‘readers’ that transduce the signal from the presence or absence of PTMs in specific cellular contexts. We provide background on PTMs and their complexes, review the known combinatorial function of PTMs, and assess the value and limitations of common approaches to measure combinatorial PTMs. This review serves as both a reference and a path forward to investigate combinatorial PTM functions, discover new synergies, and gather additional evidence supporting that combinations of histone PTMs are the central currency of chromatin-mediated regulation of the genome.
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Nie, Litong, Mingrui Zhu, Shengnan Sun, Linhui Zhai, Zhixiang Wu, Lili Qian, and Minjia Tan. "An optimization of the LC-MS/MS workflow for deep proteome profiling on an Orbitrap Fusion." Analytical Methods 8, no. 2 (2016): 425–34. http://dx.doi.org/10.1039/c5ay01900a.
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Linthwaite, Victoria L., and Martin J. Cann. "A methodology for carbamate post-translational modification discovery and its application in Escherichia coli." Interface Focus 11, no. 2 (February 12, 2021): 20200028. http://dx.doi.org/10.1098/rsfs.2020.0028.
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Carbon dioxide can influence cell phenotypes through the modulation of signalling pathways. CO 2 regulates cellular processes as diverse as metabolism, cellular homeostasis, chemosensing and pathogenesis. This diversity of regulated processes suggests a broadly conserved mechanism for CO 2 interactions with diverse cellular targets. CO 2 is generally unreactive but can interact with neutral amines on protein under normal intracellular conditions to form a carbamate post-translational modification (PTM). We have previously demonstrated the presence of this PTM in a subset of protein produced by the model plant species Arabidopsis thaliana . Here, we describe a detailed methodology for identifying new carbamate PTMs in an extracted soluble proteome under biologically relevant conditions. We apply this methodology to the soluble proteome of the model prokaryote Escherichia coli and identify new carbamate PTMs . The application of this methodology, therefore, supports the hypothesis that the carbamate PTM is both more widespread in biology than previously suspected and may represent a broadly relevant mechanism for CO 2 –protein interactions.
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Wang, Minghui, Yujie Jiang, and Xiaoyi Xu. "A novel method for predicting post-translational modifications on serine and threonine sites by using site-modification network profiles." Molecular BioSystems 11, no. 11 (2015): 3092–100. http://dx.doi.org/10.1039/c5mb00384a.
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HE, LIN, XI HAN, and BIN MA. "DE NOVO SEQUENCING WITH LIMITED NUMBER OF POST-TRANSLATIONAL MODIFICATIONS PER PEPTIDE." Journal of Bioinformatics and Computational Biology 11, no. 04 (July 16, 2013): 1350007. http://dx.doi.org/10.1142/s0219720013500078.
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De novo sequencing derives the peptide sequence from a tandem mass spectrum without the assistance of protein databases. This analysis has been indispensable for the identification of novel or modified peptides in a biological sample. Currently, the speed of de novo sequencing algorithms is not heavily affected by the number of post-translational modification (PTM) types in consideration. However, the accuracy of the algorithms can be degraded due to the increased search space. Most peptides in a proteomics research contain only a small number of PTMs per peptide, yet the types of PTMs can come from a large number of choices. Therefore, it is desirable to include a large number of PTM types in a de novo sequencing algorithm, yet to limit the number of PTM occurrences in each peptide to increase the accuracy. In this paper, we present an efficient de novo sequencing algorithm, DeNovoPTM, for such a purpose. The implemented software is downloadable from http://www.cs.uwaterloo.ca/~l22he/denovo_ptm .
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Blee, Tajekesa K. P., Nicola K. Gray, and Matthew Brook. "Modulation of the cytoplasmic functions of mammalian post-transcriptional regulatory proteins by methylation and acetylation: a key layer of regulation waiting to be uncovered?" Biochemical Society Transactions 43, no. 6 (November 27, 2015): 1285–95. http://dx.doi.org/10.1042/bst20150172.
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Post-transcriptional control of gene expression is critical for normal cellular function and viability and many of the proteins that mediate post-transcriptional control are themselves subject to regulation by post-translational modification (PTM), e.g. phosphorylation. However, proteome-wide studies are revealing new complexities in the PTM status of mammalian proteins, in particular large numbers of novel methylated and acetylated residues are being identified. Here we review studied examples of methylation/acetylation-dependent regulation of post-transcriptional regulatory protein (PTRP) function and present collated PTM data that points to the huge potential for regulation of mRNA fate by these PTMs.
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Liu, Hui-Fang, and Rong Liu. "Structure-based prediction of post-translational modification cross-talk within proteins using complementary residue- and residue pair-based features." Briefings in Bioinformatics 21, no. 2 (January 11, 2019): 609–20. http://dx.doi.org/10.1093/bib/bby123.
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Abstract Post-translational modification (PTM)-based regulation can be mediated not only by the modification of a single residue but also by the interplay of different modifications. Accurate prediction of PTM cross-talk is a highly challenging issue and is in its infant stage. Especially, less attention has been paid to the structural preferences (except intrinsic disorder and spatial proximity) of cross-talk pairs and the characteristics of individual residues involved in cross-talk, which may restrict the improvement of the prediction accuracy. Here we report a structure-based algorithm called PCTpred to improve the PTM cross-talk prediction. The comprehensive residue- and residue pair-based features were designed for paired PTM sites at the sequence and structural levels. Through feature selection, we reserved 23 newly introduced descriptors and 3 traditional descriptors to develop a sequence-based predictor PCTseq and a structure-based predictor PCTstr, both of which were integrated to construct our final prediction model. According to pair- and protein-based evaluations, PCTpred yielded area under the curve values of approximately 0.9 and 0.8, respectively. Even when removing the distance preference of samples or using the input of modeled structures, our prediction performance was maintained or moderately reduced. PCTpred displayed stable and reliable improvements over the state-of-the-art methods based on various evaluations. The source code and data set are freely available at https://github.com/Liulab-HZAU/PCTpred or http://liulab.hzau.edu.cn/PCTpred/.
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Lassak, Jürgen, Franziska Koller, Ralph Krafczyk, and Wolfram Volkwein. "Exceptionally versatile – arginine in bacterial post-translational protein modifications." Biological Chemistry 400, no. 11 (November 26, 2019): 1397–427. http://dx.doi.org/10.1515/hsz-2019-0182.
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AbstractPost-translational modifications (PTM) are the evolutionary solution to challenge and extend the boundaries of genetically predetermined proteomic diversity. As PTMs are highly dynamic, they also hold an enormous regulatory potential. It is therefore not surprising that out of the 20 proteinogenic amino acids, 15 can be post-translationally modified. Even the relatively inert guanidino group of arginine is subject to a multitude of mostly enzyme mediated chemical changes. The resulting alterations can have a major influence on protein function. In this review, we will discuss how bacteria control their cellular processes and develop pathogenicity based on post-translational protein-arginine modifications.
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Kissel, T., S. Reijm, LM Slot, M. Cavallari, CM Wortel, RD Vergroesen, G. Stoeken-Rijsbergen, et al. "Antibodies and B cells recognising citrullinated proteins display a broad cross-reactivity towards other post-translational modifications." Annals of the Rheumatic Diseases 79, no. 4 (February 10, 2020): 472–80. http://dx.doi.org/10.1136/annrheumdis-2019-216499.
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ObjectiveAutoantibodies against antigens carrying distinct post-translational modifications (PTMs), such as citrulline, homocitrulline or acetyllysine, are hallmarks of rheumatoid arthritis (RA). The relation between these anti-modified protein antibody (AMPA)-classes is poorly understood as is the ability of different PTM-antigens to activate B-cell receptors (BCRs) directed against citrullinated proteins (CP). Insights into the nature of PTMs able to activate such B cells are pivotal to understand the ‘evolution’ of the autoimmune response conceivable underlying the disease. Here, we investigated the cross-reactivity of monoclonal AMPA and the ability of different types of PTM-antigens to activate CP-reactive BCRs.MethodsBCR sequences from B cells isolated using citrullinated or acetylated antigens were used to produce monoclonal antibodies (mAb) followed by a detailed analysis of their cross-reactivity towards PTM-antigens. Ramos B-cell transfectants expressing CP-reactive IgG BCRs were generated and their activation on stimulation with PTM-antigens investigated.ResultsMost mAbs were highly cross-reactive towards multiple PTMs, while no reactivity was observed to the unmodified controls. B cells carrying CP-reactive BCRs showed activation on stimulation with various types of PTM-antigens.ConclusionsOur study illustrates that AMPA exhibit a high cross-reactivity towards at least two PTMs indicating that their recognition pattern is not confined to one type of modification. Furthermore, our data show that CP-reactive B cells are not only activated by citrullinated, but also by carbamylated and/or acetylated antigens. These data are vital for the understanding of the breach of B-cell tolerance against PTM-antigens and the possible contribution of these antigens to RA-pathogenesis.
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Song, Lei, and Zhao-Qing Luo. "Post-translational regulation of ubiquitin signaling." Journal of Cell Biology 218, no. 6 (April 18, 2019): 1776–86. http://dx.doi.org/10.1083/jcb.201902074.
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Ubiquitination regulates many essential cellular processes in eukaryotes. This post-translational modification (PTM) is typically achieved by E1, E2, and E3 enzymes that sequentially catalyze activation, conjugation, and ligation reactions, respectively, leading to covalent attachment of ubiquitin, usually to lysine residues of substrate proteins. Ubiquitin can also be successively linked to one of the seven lysine residues on ubiquitin to form distinctive forms of polyubiquitin chains, which, depending upon the lysine used and the length of the chains, dictate the fate of substrate proteins. Recent discoveries revealed that this ubiquitin code is further expanded by PTMs such as phosphorylation, acetylation, deamidation, and ADP-ribosylation, on ubiquitin, components of the ubiquitination machinery, or both. These PTMs provide additional regulatory nodes to integrate development or insulting signals with cellular homeostasis. Understanding the precise roles of these PTMs in the regulation of ubiquitin signaling will provide new insights into the mechanisms and treatment of various human diseases linked to ubiquitination, including neurodegenerative diseases, cancer, infection, and immune disorders.
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Brewster, Richard C., and Alison N. Hulme. "Halomethyl-Triazoles for Rapid, Site-Selective Protein Modification." Molecules 26, no. 18 (September 8, 2021): 5461. http://dx.doi.org/10.3390/molecules26185461.
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Post-translational modifications (PTMs) are used by organisms to control protein structure and function after protein translation, but their study is complicated and their roles are not often well understood as PTMs are difficult to introduce onto proteins selectively. Designing reagents that are both good mimics of PTMs, but also only modify select amino acid residues in proteins is challenging. Frequently, both a chemical warhead and linker are used, creating a product that is a misrepresentation of the natural modification. We have previously shown that biotin-chloromethyl-triazole is an effective reagent for cysteine modification to give S-Lys derivatives where the triazole is a good mimic of natural lysine acylation. Here, we demonstrate both how the reactivity of the alkylating reagents can be increased and how the range of triazole PTM mimics can be expanded. These new iodomethyl-triazole reagents are able to modify a cysteine residue on a histone protein with excellent selectivity in 30 min to give PTM mimics of acylated lysine side-chains. Studies on the more complicated, folded protein SCP-2L showed promising reactivity, but also suggested the halomethyl-triazoles are potent alkylators of methionine residues.
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Scruggs, Sarah B., Nobel C. Zong, Ding Wang, Enrico Stefani, and Peipei Ping. "Post-translational modification of cardiac proteasomes: functional delineation enabled by proteomics." American Journal of Physiology-Heart and Circulatory Physiology 303, no. 1 (July 1, 2012): H9—H18. http://dx.doi.org/10.1152/ajpheart.00189.2012.
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Proteasomes are ubiquitously expressed multicatalytic complexes that serve as key regulators of protein homeostasis. There are several lines of evidence indicating that proteasomes exist in heterogeneous subpopulations in cardiac muscle, differentiated, in part, by post-translational modifications (PTMs). PTMs regulate numerous facets of proteasome function, including catalytic activities, complex assembly, interactions with associating partners, subcellular localization, substrate preference, and complex turnover. Classical technologies used to identify PTMs on proteasomes have lacked the ability to determine site specificity, quantify stoichiometry, and perform large-scale, multi-PTM analysis. Recent advancements in proteomic technologies have largely overcome these limitations. We present here a discussion on the importance of PTMs in modulating proteasome function in cardiac physiology and pathophysiology, followed by the presentation of a state-of-the-art proteomic workflow for identifying and quantifying PTMs of cardiac proteasomes.
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Christensen, Brian, Torben E. Petersen, and Esben S. Sørensen. "Post-translational modification and proteolytic processing of urinary osteopontin." Biochemical Journal 411, no. 1 (March 13, 2008): 53–61. http://dx.doi.org/10.1042/bj20071021.
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OPN (osteopontin) is a highly phosphorylated glycoprotein present in many tissues and body fluids. In urine, OPN is a potent inhibitor of nucleation, growth and aggregation of calcium oxalate crystals, suggesting that it has a role in the prevention of renal stone formation. The role of OPN in nephrolithiasis is, however, somewhat unclear, as it may also be involved in urinary stone formation, and it has been identified among the major protein components of renal calculi. Most likely, the function of OPN in urine is dependent on the highly anionic character of the protein. Besides a very high content of aspartic and glutamic residues, OPN is subjected to significant PTM (post-translational modification), such as phosphorylation, sulfation and glycosylation, which may function as regulatory switches in promotion or inhibition of mineralization. In the present study, we have characterized the PTMs of intact human urinary OPN and N-terminal fragments thereof. MS analysis showed a mass of 37.7 kDa for the intact protein. Enzymatic dephosphorylation and peptide mass analyses demonstrated that the protein contains approximately eight phosphate groups distributed over 30 potential phosphorylation sites. In addition, one sulfated tyrosine and five O-linked glycosylations were identified in OPN, whereas no N-linked glycans were detected. Peptide mapping and immunoblotting using different monoclonal antibodies showed that the N-terminal fragments present in urine are generated by proteolytic cleavage at Arg228–Leu229 and Tyr230–Lys231.
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Sun, Dongdong, Minghui Wang, and Ao Li. "MPTM: A tool for mining protein post-translational modifications from literature." Journal of Bioinformatics and Computational Biology 15, no. 05 (October 2017): 1740005. http://dx.doi.org/10.1142/s0219720017400054.
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Due to the importance of post-translational modifications (PTMs) in human health and diseases, PTMs are regularly reported in the biomedical literature. However, the continuing and rapid pace of expansion of this literature brings a huge challenge for researchers and database curators. Therefore, there is a pressing need to aid them in identifying relevant PTM information more efficiently by using a text mining system. So far, only a few web servers are available for mining information of a very limited number of PTMs, which are based on simple pattern matching or pre-defined rules. In our work, in order to help researchers and database curators easily find and retrieve PTM information from available text, we have developed a text mining tool called MPTM, which extracts and organizes valuable knowledge about 11 common PTMs from abstracts in PubMed by using relations extracted from dependency parse trees and a heuristic algorithm. It is the first web server that provides literature mining service for hydroxylation, myristoylation and GPI-anchor. The tool is also used to find new publications on PTMs from PubMed and uncovers potential PTM information by large-scale text analysis. MPTM analyzes text sentences to identify protein names including substrates and protein-interacting enzymes, and automatically associates them with the UniProtKB protein entry. To facilitate further investigation, it also retrieves PTM-related information, such as human diseases, Gene Ontology terms and organisms from the input text and related databases. In addition, an online database (MPTMDB) with extracted PTM information and a local MPTM Lite package are provided on the MPTM website. MPTM is freely available online at http://bioinformatics.ustc.edu.cn/mptm/ and the source codes are hosted on GitHub: https://github.com/USTC-HILAB/MPTM .
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Li, Ginny X. H., Christine Vogel, and Hyungwon Choi. "PTMscape: an open source tool to predict generic post-translational modifications and map modification crosstalk in protein domains and biological processes." Molecular Omics 14, no. 3 (2018): 197–209. http://dx.doi.org/10.1039/c8mo00027a.
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Wang, Binghua, Minghui Wang, Yujie Jiang, Dongdong Sun, and Xiaoyi Xu. "A novel network-based computational method to predict protein phosphorylation on tyrosine sites." Journal of Bioinformatics and Computational Biology 13, no. 06 (December 2015): 1542005. http://dx.doi.org/10.1142/s0219720015420056.
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Phosphorylation plays a great role in regulating a variety of cellular processes and the identification of tyrosine phosphorylation sites is fundamental for understanding the post-translational modification (PTM) regulation processes. Although a lot of computational methods have been developed, most of them only concern local sequence information and few studies focus on the tyrosine sites with in situ PTM information, which refers to different types of PTM occurring on the same modification site. In this study, by constructing the site-modification network that efficiently incorporates in situ PTM information, we introduce a novel network-based computational method, site-modification network-based inference (SMNBI) to predict tyrosine phosphorylation. In order to verify the effectiveness of the proposed method, we compare it with other network-based computational methods. The results clearly show the superior performance of SMNBI. Besides, we extensively compare SMNBI with other sequence-based methods including SVM and Bayesian decision theory. The evaluation demonstrates the power of site-modification network in predicting tyrosine phosphorylation. The proposed method is freely available at http://bioinformatics.ustc.edu.cn/smnbi/ .
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Ryan, Philip, Mingming Xu, Andrew K. Davey, George D. Mellick, and Santosh Rudrawar. "Design, Synthesis, and Biological Evaluation of Bimodal Glycopeptides as Inhibitors of Neurotoxic Protein Aggregation." Proceedings 22, no. 1 (August 7, 2019): 32. http://dx.doi.org/10.3390/proceedings2019022032.
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Kungulovski, Goran, and Albert Jeltsch. "Quality of histone modification antibodies undermines chromatin biology research." F1000Research 4 (October 28, 2015): 1160. http://dx.doi.org/10.12688/f1000research.7265.1.
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Histone post-translational modification (PTM) antibodies are essential research reagents in chromatin biology. However, they suffer from variable properties and insufficient documentation of quality. Antibody manufacturers and vendors should provide detailed lot-specific documentation of quality, rendering further quality checks by end-customers unnecessary. A shift from polyclonal antibodies towards sustainable reagents like monoclonal or recombinant antibodies or histone binding domains would help to improve the reproducibility of experimental work in this field.
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Kungulovski, Goran, and Albert Jeltsch. "Quality of histone modification antibodies undermines chromatin biology research." F1000Research 4 (November 24, 2015): 1160. http://dx.doi.org/10.12688/f1000research.7265.2.
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Histone post-translational modification (PTM) antibodies are essential research reagents in chromatin biology. However, they suffer from variable properties and insufficient documentation of quality. Antibody manufacturers and vendors should provide detailed lot-specific documentation of quality, rendering further quality checks by end-customers unnecessary. A shift from polyclonal antibodies towards sustainable reagents like monoclonal or recombinant antibodies or histone binding domains would help to improve the reproducibility of experimental work in this field.
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Li, Fuyi, Cunshuo Fan, Tatiana T. Marquez-Lago, André Leier, Jerico Revote, Cangzhi Jia, Yan Zhu, et al. "PRISMOID: a comprehensive 3D structure database for post-translational modifications and mutations with functional impact." Briefings in Bioinformatics 21, no. 3 (June 4, 2019): 1069–79. http://dx.doi.org/10.1093/bib/bbz050.
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Abstract Post-translational modifications (PTMs) play very important roles in various cell signaling pathways and biological process. Due to PTMs’ extremely important roles, many major PTMs have been studied, while the functional and mechanical characterization of major PTMs is well documented in several databases. However, most currently available databases mainly focus on protein sequences, while the real 3D structures of PTMs have been largely ignored. Therefore, studies of PTMs 3D structural signatures have been severely limited by the deficiency of the data. Here, we develop PRISMOID, a novel publicly available and free 3D structure database for a wide range of PTMs. PRISMOID represents an up-to-date and interactive online knowledge base with specific focus on 3D structural contexts of PTMs sites and mutations that occur on PTMs and in the close proximity of PTM sites with functional impact. The first version of PRISMOID encompasses 17 145 non-redundant modification sites on 3919 related protein 3D structure entries pertaining to 37 different types of PTMs. Our entry web page is organized in a comprehensive manner, including detailed PTM annotation on the 3D structure and biological information in terms of mutations affecting PTMs, secondary structure features and per-residue solvent accessibility features of PTM sites, domain context, predicted natively disordered regions and sequence alignments. In addition, high-definition JavaScript packages are employed to enhance information visualization in PRISMOID. PRISMOID equips a variety of interactive and customizable search options and data browsing functions; these capabilities allow users to access data via keyword, ID and advanced options combination search in an efficient and user-friendly way. A download page is also provided to enable users to download the SQL file, computational structural features and PTM sites’ data. We anticipate PRISMOID will swiftly become an invaluable online resource, assisting both biologists and bioinformaticians to conduct experiments and develop applications supporting discovery efforts in the sequence–structural–functional relationship of PTMs and providing important insight into mutations and PTM sites interaction mechanisms. The PRISMOID database is freely accessible at http://prismoid.erc.monash.edu/. The database and web interface are implemented in MySQL, JSP, JavaScript and HTML with all major browsers supported.
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Zhu, Yi, and Gerald W. Hart. "Nutrient regulation of the flow of genetic information by O-GlcNAcylation." Biochemical Society Transactions 49, no. 2 (March 26, 2021): 867–80. http://dx.doi.org/10.1042/bst20200769.
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O-linked-β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification (PTM) that is actively added to and removed from thousands of intracellular proteins. As a PTM, O-GlcNAcylation tunes the functions of a protein in various ways, such as enzymatic activity, transcriptional activity, subcellular localization, intermolecular interactions, and degradation. Its regulatory roles often interplay with the phosphorylation of the same protein. Governed by ‘the Central Dogma’, the flow of genetic information is central to all cellular activities. Many proteins regulating this flow are O-GlcNAc modified, and their functions are tuned by the cycling sugar. Herein, we review the regulatory roles of O-GlcNAcylation on the epigenome, in DNA replication and repair, in transcription and in RNA processing, in protein translation and in protein turnover.
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Mallela, Abhishek, Maulik K. Nariya, and Eric J. Deeds. "Crosstalk and ultrasensitivity in protein degradation pathways." PLOS Computational Biology 16, no. 12 (December 28, 2020): e1008492. http://dx.doi.org/10.1371/journal.pcbi.1008492.
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Protein turnover is vital to cellular homeostasis. Many proteins are degraded efficiently only after they have been post-translationally “tagged” with a polyubiquitin chain. Ubiquitylation is a form of Post-Translational Modification (PTM): addition of a ubiquitin to the chain is catalyzed by E3 ligases, and removal of ubiquitin is catalyzed by a De-UBiquitylating enzyme (DUB). Nearly four decades ago, Goldbeter and Koshland discovered that reversible PTM cycles function like on-off switches when the substrates are at saturating concentrations. Although this finding has had profound implications for the understanding of switch-like behavior in biochemical networks, the general behavior of PTM cycles subject to synthesis and degradation has not been studied. Using a mathematical modeling approach, we found that simply introducing protein turnover to a standard modification cycle has profound effects, including significantly reducing the switch-like nature of the response. Our findings suggest that many classic results on PTM cycles may not hold in vivo where protein turnover is ubiquitous. We also found that proteins sharing an E3 ligase can have closely related changes in their expression levels. These results imply that it may be difficult to interpret experimental results obtained from either overexpressing or knocking down protein levels, since changes in protein expression can be coupled via E3 ligase crosstalk. Understanding crosstalk and competition for E3 ligases will be key in ultimately developing a global picture of protein homeostasis.
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Sun, Chen-Fan, Yong-Quan Li, and Xu-Ming Mao. "Regulation of Protein Post-Translational Modifications on Metabolism of Actinomycetes." Biomolecules 10, no. 8 (July 29, 2020): 1122. http://dx.doi.org/10.3390/biom10081122.
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Protein post-translational modification (PTM) is a reversible process, which can dynamically regulate the metabolic state of cells through regulation of protein structure, activity, localization or protein–protein interactions. Actinomycetes are present in the soil, air and water, and their life cycle is strongly determined by environmental conditions. The complexity of variable environments urges Actinomycetes to respond quickly to external stimuli. In recent years, advances in identification and quantification of PTMs have led researchers to deepen their understanding of the functions of PTMs in physiology and metabolism, including vegetative growth, sporulation, metabolite synthesis and infectivity. On the other hand, most donor groups for PTMs come from various metabolites, suggesting a complex association network between metabolic states, PTMs and signaling pathways. Here, we review the mechanisms and functions of PTMs identified in Actinomycetes, focusing on phosphorylation, acylation and protein degradation in an attempt to summarize the recent progress of research on PTMs and their important role in bacterial cellular processes.
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Klings, Elizabeth S., Adam Odhiambo, David Perlman, Hua Huang, Catherine Costello, Harrison W. Farber, Mark McComb, and Martin H. Steinberg. "Identification of Oxidative Post-Translational Modifications on Plasma Albumin in Patients with Pulmonary Hypertension of Sickle Cell Anemia." Blood 108, no. 11 (November 16, 2006): 1215. http://dx.doi.org/10.1182/blood.v108.11.1215.1215.
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Abstract Pulmonary hypertension (PH) in sickle cell anemia (SCA) is characterized by decreased nitric oxide bioavailability; which may, in part, be related to increased oxidative stress. It is possible that via protein post-translational modifications, oxidants are able to affect both protein structure and function. We hypothesized that, in patients with SCA and PH, oxidative post-translational modifications occur on plasma proteins and are important in disease pathogenesis. To examine this hypothesis, we chose to determine if oxidative post-translational modifications occur in a large-abundance protein, albumin, as a reflection of the presence of more widespread protein oxidative damage. Plasma was obtained from subjects with:SCA and PH (n=5);SCA steady-state without PH (n=4);Pulmonary Arterial Hypertension (PAH) (n=4);no evidence of cardiopulmonary disease (n=4). Platelet-poor plasma was separated into albumin-enriched and albumin-depleted fractions. The albumin-enriched fraction was subjected to proteolytic digestion by trypsin and studied by matrix assisted laser desorption ionization (MALDI) mass spectroscopy (MS) and liquid chromatography (LC)-MS/MS tandem mass spectrometry. Proteomics analyses were performed on all samples and post-translational modifications characterized by MS/MS. Results were confirmed by Western and dot-blot analysis using commercially available antibodies. In the albumin fraction, we identified peaks of differential post-translational modification on albumin peptide 146–159 only in PAH and SCA and PH samples; this PTM was identified to be a malondialdehyde adduct. The presence of a malondialdehyde adduct on albumin was confirmed by LC-MS/MS and Western analysis. We have identified a malondialdehyde adduct in plasma albumin that appears to be a common link between PH related to SCA and PAH. This finding supports the notion that oxidative stress modulates the pathogenesis of PH of SCA and suggests that this and other post-translational modifications may be important biomarkers of disease.
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Tsikas, Dimitrios. "Post-translational modifications (PTM): analytical approaches, signaling, physiology and pathophysiology—part I." Amino Acids 53, no. 4 (April 2021): 485–87. http://dx.doi.org/10.1007/s00726-021-02984-y.
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Lira-Navarrete, Erandi, and Ramon Hurtado-Guerrero. "A perspective on structural and mechanistic aspects of protein O-fucosylation." Acta Crystallographica Section F Structural Biology Communications 74, no. 8 (July 26, 2018): 443–50. http://dx.doi.org/10.1107/s2053230x18004788.
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Protein O-fucosylation is an important post-translational modification (PTM) found in cysteine-rich repeats in proteins. Protein O-fucosyltransferases 1 and 2 (PoFUT1 and PoFUT2) are the enzymes responsible for this PTM and selectively glycosylate specific residues in epidermal growth factor-like (EGF) repeats and thrombospondin type I repeats (TSRs), respectively. Within the past six years, crystal structures of both enzymes have been reported, revealing important information on how they recognize protein substrates and achieve catalysis. Here, the structural information available today is summarized and how PoFUT1 and PoFUT2 employ different catalytic mechanisms is discussed.
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Liu, Yu, Minghui Wang, Jianing Xi, Fenglin Luo, and Ao Li. "PTM-ssMP: A Web Server for Predicting Different Types of Post-translational Modification Sites Using Novel Site-specific Modification Profile." International Journal of Biological Sciences 14, no. 8 (2018): 946–56. http://dx.doi.org/10.7150/ijbs.24121.
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Klings, Elizabeth S., Stephen Whelan, Roger Theberge, Jean L. Spencer, Martin H. Steinberg, Catherine E. Costello, and Mark E. McComb. "Identification Of Protein and Post Translational Modification Markers Of Pulmonary Vasculopathy In Sickle Cell Disease." Blood 122, no. 21 (November 15, 2013): 2233. http://dx.doi.org/10.1182/blood.v122.21.2233.2233.
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Abstract Pulmonary hypertension (PH), an independent risk factor for mortality in sickle cell disease (SCD), has epidemiologic links to systemic complications such as leg ulcers, priapism and renal disease suggestive of a diffuse vasculopathy. The pathogenesis of SCD related vasculopathy is unclear but altered redox biology is thought to be an important disease modifier. One potential mechanism by which this occurs is via plasma protein post-translational modifications (PTMs). Here we aim to identify a plasma protein and PTM signature profile reflective of PH and pulmonary vasculopathy related to SCD. By targeting both protein and PTM changes, we hoped to enhance the specificity of detecting biomarkers. To control for sex-related protein changes, we limited the present study to females. We obtained peripheral blood samples from 1) SCD patients with a normal echocardiogram (n=10); 2) SCD patients with PH diagnosed by right heart catheterization (n=6) or a tricuspid regurgitant jet velocity > 2.5 m/sec suggestive of pulmonary vasculopathy (n=4) (total n=10); 3) Age- and racially- matched HbAA volunteers (n=11). Plasma was depleted of high abundance proteins using accepted protocols. We performed differential proteomic analysis of plasma and abundant protein-depleted plasma, and differential analysis of PTMs on abundant plasma proteins. Plasma was subjected to trypsin digestion and the peptides were analyzed by differential label-free LCMS/MS. Peptide and protein identification was performed utilizing Proteome Discoverer (Thermo-Fisher) and Mascot (Matrix Science). Data analysis was conducted using the Trans-Proteomics-Pipeline (ISB), Scaffold (Proteome Software), Progenesis LCMS (Nonlinear Dynamics) and STRAP-PTM (in-house). LCMS/MS analysis of the entire plasma proteome revealed more than 2,500 changes in peptide expression between groups and almost 400 peptides which contained PTMs differentiating the SCD patients from the normal volunteers (ANOVA p< 0.05). Analyses indicated significant fold changes for a large group of known plasma protein markers associated with cardiovascular disease, redox biology and metabolism, and the inflammatory host response including alpha-2-HS glycoproteins, ceruloplasmin, apolipoprotein E, transthyretin, kininogen, carbonic anhydrase, angiotensinogen, and complement C4. We also observed changes in the PTMs of several plasma proteins including human albumin, particularly S-cysteinylation on Cys-34, and significant modifications by lipid peroxidation and glycation-end products, such as malonyldialdehyde, 4-hydroxynonenal, and hexose. Further refinement of the data to look only at the SCD samples demonstrated an increased frequency of oxidative PTMs on proteins and peptides from those with PH or an elevated TRV. Additionally, we identified 19 peptides which were distinct in the PH group compared with SCD patients with normal cardiopulmonary function. The corresponding proteins were identified as those important in redox biology, nitric oxide and nitrite signaling, and vasodilatation. This suggests that utilization of proteomics technologies may help to identify unique biomarkers reflective of disease progression and pathogenesis which may help to risk stratify patients and assess response to therapy. Disclosures: No relevant conflicts of interest to declare.