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Littérature scientifique sur le sujet « PPIasa »

Auteur : Grafiati

Publié le 4 juin 2021

Mis à jour le 1 février 2022

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Articles de revues sur le sujet "PPIasa"

Skagia, Aggeliki, Eleni Vezyri, Konstantinos Grados, Anastasia Venieraki, Michael Karpusas, Panagiotis Katinakis et Maria Dimou. « Structure-Function Analysis of the Periplasmic Escherichia coli Cyclophilin PpiA in Relation to Biofilm Formation ». Journal of Molecular Microbiology and Biotechnology 27, n^o 4 (2017) : 228–36. http://dx.doi.org/10.1159/000478858.

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The presence of peptidyl-prolyl cis/trans isomerases (PPIases, EC: 5.2.1.8) in all domains of life indicates their biological importance. Cyclophilin PpiA, present in the periplasm of gram-negative bacteria, possesses PPIase activity but its physiological functions are still not clearly defined. Here, we demonstrate that the ΔppiA deletion strain from Escherichia coli exhibits an increased ability for biofilm formation and enhanced swimming motility compared to the wild-type strain. To identify structural features of PpiA which are necessary for the negative modulation of biofilm formation, we constructed a series of mutant PpiA proteins using a combination of error-prone and site-directed mutagenesis approaches. We show that the negative effect of PpiA on biofilm formation is not dependent on its PPIase activity, since PpiA mutants with a reduced PPIase activity are able to complement the ΔppiA strain during biofilm growth.

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Obi, Ikenna R., Roland Nordfelth et Matthew S. Francis. « Varying dependency of periplasmic peptidylprolyl cis–trans isomerases in promoting Yersinia pseudotuberculosis stress tolerance and pathogenicity ». Biochemical Journal 439, n^o 2 (28 septembre 2011) : 321–32. http://dx.doi.org/10.1042/bj20110767.

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Periplasmic PPIases (peptidylprolyl cis–trans isomerases) catalyse the cis–trans isomerization of peptidyl-prolyl bonds, which is a rate-limiting step during protein folding. We demonstrate that the surA, ppiA, ppiD, fkpA and fklB alleles each encode a periplasmic PPIase in the bacterial pathogen Yersinia pseudotuberculosis. Of these, four were purified to homogeneity. Purified SurA, FkpA and FklB, but not PpiD, displayed detectable PPIase activity in vitro. Significantly, only Y. pseudotuberculosis lacking surA caused drastic alterations to the outer membrane protein profile and FA (fatty acid) composition. They also exhibited aberrant cellular morphology, leaking LPS (lipopolysaccharide) into the extracellular environment. The SurA PPIase is therefore most critical for maintaining Y. pseudotuberculosis envelope integrity during routine culturing. On the other hand, bacteria lacking either surA or all of the genes ppiA, ppiD, fkpA and fklB were sensitive to hydrogen peroxide and were attenuated in mice infections. Thus Y. pseudotuberculosis exhibits both SurA-dependent and -independent requirements for periplasmic PPIase activity to ensure in vivo survival and a full virulence effect in a mammalian host.

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Stifani, Stefano. « The Multiple Roles of Peptidyl Prolyl Isomerases in Brain Cancer ». Biomolecules 8, n^o 4 (11 octobre 2018) : 112. http://dx.doi.org/10.3390/biom8040112.

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Peptidyl prolyl isomerases (PPIases) are broadly expressed enzymes that accelerate the cis-trans isomerization of proline peptide bonds. The most extensively studied PPIase family member is protein interacting with never in mitosis A1 (PIN1), which isomerizes phosphorylated serine/threonine–proline bonds. By catalyzing this specific cis-trans isomerization, PIN1 can alter the structure of its target proteins and modulate their activities in a number of different ways. Many proteins are targets of proline-directed phosphorylation and thus PIN1-mediated isomerization of proline bonds represents an important step in the regulation of a variety of cellular mechanisms. Numerous other proteins in addition to PIN1 are endowed with PPIase activity. These include other members of the parvulin family to which PIN1 belongs, such as PIN4, as well as several cyclophilins and FK506-binding proteins. Unlike PIN1, however, these other PPIases do not isomerize phosphorylated serine/threonine–proline bonds and have different substrate specificities. PIN1 and other PPIases are overexpressed in many types of cancer and have been implicated in various oncogenic processes. This review will discuss studies providing evidence for multiple roles of PIN1 and other PPIases in glioblastoma and medulloblastoma, the most frequent adult and pediatric primary brain tumors.

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Klein, Gracjana, Pawel Wojtkiewicz, Daria Biernacka, Anna Stupak, Patrycja Gorzelak et Satish Raina. « Identification of Substrates of Cytoplasmic Peptidyl-Prolyl Cis/Trans Isomerases and Their Collective Essentiality in Escherichia Coli ». International Journal of Molecular Sciences 21, n^o 12 (13 juin 2020) : 4212. http://dx.doi.org/10.3390/ijms21124212.

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Protein folding often requires molecular chaperones and folding catalysts, such as peptidyl-prolyl cis/trans isomerases (PPIs). The Escherichia coli cytoplasm contains six well-known PPIs, although a requirement of their PPIase activity, the identity of their substrates and relative enzymatic contribution is unknown. Thus, strains lacking all periplasmic and one of the cytoplasmic PPIs were constructed. Measurement of their PPIase activity revealed that PpiB is the major source of PPIase activity in the cytoplasm. Furthermore, viable Δ6ppi strains could be constructed only on minimal medium in the temperature range of 30–37 °C, but not on rich medium. To address the molecular basis of essentiality of PPIs, proteins that aggregate in their absence were identified. Next, wild-type and putative active site variants of FkpB, FklB, PpiB and PpiC were purified and in pull-down experiments substrates specific to each of these PPIs identified, revealing an overlap of some substrates. Substrates of PpiC were validated by immunoprecipitations using extracts from wild-type and PpiC-H81A strains carrying a 3xFLAG-tag appended to the C-terminal end of the ppiC gene on the chromosome. Using isothermal titration calorimetry, RpoE, RseA, S2, and AhpC were established as FkpB substrates and PpiC’s PPIase activity was shown to be required for interaction with AhpC.

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Reffuveille, Fany, Nathalie Connil, Maurizio Sanguinetti, Brunella Posteraro, Sylvie Chevalier, Yanick Auffray et Alain Rince. « Involvement of Peptidylprolylcis/transIsomerases in Enterococcus faecalis Virulence ». Infection and Immunity 80, n^o 5 (13 février 2012) : 1728–35. http://dx.doi.org/10.1128/iai.06251-11.

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ABSTRACTPeptidylprolylcis/transisomerases (PPIases) are enzymes involved in protein folding. Analysis of the genome sequence ofEnterococcus faecalisV583 allowed for identification of 3 PPIases carrying genes.ef2898encodes an intracellular PPIase which was not shown to be important for theE. faecalisstress response or virulence. The other two PPIases, the parvulin family rotamase EF0685 and the cyclophilin family member EF1534, are expected to be surface-exposed proteins. They were shown to be important for virulence and resistance to NaCl. A Δef0685Δef1534mutant was also more resistant to oxidative stress, was able to grow under a high manganese concentration, and showed altered resistance to ampicillin and quinolone antibiotics.

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Trémillon, Nicolas, Eric Morello, Daniel Llull, Rabia Mazmouz, Jean-Jacques Gratadoux, Alain Guillot, Marie-Pierre Chapot-Chartier et al. « PpiA, a Surface PPIase of the Cyclophilin Family in Lactococcus lactis ». PLoS ONE 7, n^o 3 (19 mars 2012) : e33516. http://dx.doi.org/10.1371/journal.pone.0033516.

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Liu, Fei, Xiao-Long Wei, Hao Li, Ji-Fu Wei, Yong-Qing Wang et Xiao-Jian Gong. « Molecular Evolution of the Vertebrate FK506 Binding Protein 25 ». International Journal of Genomics 2014 (2014) : 1–9. http://dx.doi.org/10.1155/2014/402603.

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FK506 binding proteins (FKBPs) belong to immunophilins with peptidyl-prolyl isomerases (PPIases) activity. FKBP25 (also known as FKBP3) is one of the nuclear DNA-binding proteins in the FKBPs family, which plays an important role in regulating transcription and chromatin structure. The calculation of nonsynonymous and synonymous substitution rates suggested that FKBP25 undergoes purifying selection throughout the whole vertebrate evolution. Moreover, the result of site-specific tests showed that no sites were detected under positive selection. Only one PPIase domain was detected by searching FKBP25 sequences at Pfam and SMART domain databases. Mammalian FKBP25 possess exon-intron conservation, although conservation in the whole vertebrate lineage is incomplete. The result of this study suggests that the purifying selection triggers FKBP25 evolutionary history, which allows us to discover the complete role of the PPIase domain in the interaction between FKBP25 and nuclear proteins. Moreover, intron alterations during FKBP25 evolution that regulate gene splicing may be involved in the purifying selection.

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Ahmad, Saleem, Sen Wang, Weizhong Wu, Kunlong Yang, YanFeng Zhang, Elisabeth Tumukunde, Shihua Wang et Yu Wang. « Functional Analysis of Peptidyl-prolyl cis-trans Isomerase from Aspergillus flavus ». International Journal of Molecular Sciences 20, n^o 9 (5 mai 2019) : 2206. http://dx.doi.org/10.3390/ijms20092206.

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Aspergillus flavus, a ubiquitous filamentous fungus found in soil, plants and other substrates has been reported not only as a pathogen for plants, but also a carcinogen producing fungus for human. Peptidyl-Prolyl Isomerase (PPIases) plays an important role in cell process such as protein secretion cell cycle control and RNA processing. However, the function of PPIase has not yet been identified in A. flavus. In this study, the PPIases gene from A. flavus named ppci1 was cloned into expression vector and the protein was expressed in prokaryotic expression system. Activity of recombinant ppci1 protein was particularly inhibited by FK506, CsA and rapamycin. 3D-Homology model of ppci1 has been constructed with the template, based on 59.7% amino acid similarity. The homologous recombination method was used to construct the single ppci1 gene deletion strain Δppci1. We found that, the ppci1 gene plays important roles in A. flavus growth, conidiation, and sclerotia formation, all of which showed reduction in Δppci1 and increased in conidiation compared with the wild-type and complementary strains in A. flavus. Furthermore, aflatoxin and peanut seeds infection assays indicated that ppci1 contributes to virulence of A. flavus. Furthermore, we evaluated the effect of PPIase inhibitors on A. flavus growth, whereby these were used to treat wild-type strains. We found that the growths were inhibited under every inhibitor. All, these results may provide valuable information for designing inhibitors in the controlling infections of A. flavus.

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Ren, Ping, Anne Rossettini, Vishnu Chaturvedi et Steven D. Hanes. « The Ess1 prolyl isomerase is dispensable for growth but required for virulence in Cryptococcus neoformans ». Microbiology 151, n^o 5 (1 mai 2005) : 1593–605. http://dx.doi.org/10.1099/mic.0.27786-0.

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Cryptococcus neoformans is an important human fungal pathogen that also serves as a model for studies of fungal pathogenesis. C. neoformans contains several genes encoding peptidyl-prolyl cis/trans isomerases (PPIases), enzymes that catalyse changes in the folding and conformation of target proteins. Three distinct classes of PPIases have been identified: cyclophilins, FK506-binding proteins (FKBPs) and parvulins. This paper reports the cloning and characterization of ESS1, which is believed to be the first (and probably only) parvulin-class PPIase in C. neoformans. It is shown that ESS1 from C. neoformans is structurally and functionally homologous to ESS1 from Saccharomyces cerevisiae, which encodes an essential PPIase that interacts with RNA polymerase II and plays a role in transcription. In C. neoformans, ESS1 was found to be dispensable for growth, haploid fruiting and capsule formation. However, ESS1 was required for virulence in a murine model of cryptococcosis. Loss of virulence might have been due to the defects in melanin and urease production observed in ess1 mutants, or to defects in transcription of as-yet-unidentified virulence genes. The fact that Ess1 is not essential in C. neoformans suggests that, in this organism, some of its functions might be subsumed by other prolyl isomerases, in particular, cyclophilins Cpa1 or Cpa2. This is supported by the finding that ess1 mutants were hypersensitive to cyclosporin A. C. neoformans might therefore be a useful organism in which to investigate crosstalk among different families of prolyl isomerases.

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Guan, Dan, Xiao Hu, Donghui Diao, Fang Wang et Yueping Liu. « Genome-Wide Analysis and Identification of the Aux/IAA Gene Family in Peach ». International Journal of Molecular Sciences 20, n^o 19 (23 septembre 2019) : 4703. http://dx.doi.org/10.3390/ijms20194703.

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The Auxin/indole-3-acetic acid (Aux/IAA) repressor genes down-regulate the auxin response pathway during many stages of plant and fruit development. In order to determine if and how Aux/IAAs participate in governing texture and hardness in stone fruit maturation, we identified 23 Aux/IAA genes in peach, confirmed by the presence of four conserved domains. In this work, we used fluorescence microscopy with PpIAA-GFP fusion reporters to observe their nuclear localization. We then conducted PCR-based differential expression analysis in “melting” and “stony hard” varieties of peach, and found that in the “melting” variety, nine PpIAAs exhibited peak expression in the S4-3 stage of fruit maturation, with PpIAA33 showing the highest (>120-fold) induction. The expression of six PpIAAs peaked in the S4-2 stage, with PpIAA14 expressed the most highly. Only PpIAA15/16 showed higher expression in the “stony hard” variety than in the “melting” variety, both peaking in the S3 stage. In contrast, PpIAA32 had the highest relative expression in buds, flowers, young and mature leaves, and roots. Our study provides insights into the expression patterns of Aux/IAA developmental regulators in response to auxin during fruit maturation, thus providing insight into their potential development as useful markers for quantitative traits associated with fruit phenotype.

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Thèses sur le sujet "PPIasa"

Suñé, Rodríguez Guillermo. « Identificación de proteínas que interaccionan con CypA, CypB y FKBP12 y su implicación en la toxicidad renal producida por los inmunosupresores CsA y FK506 ». Doctoral thesis, Universitat de Barcelona, 2008. http://hdl.handle.net/10803/1017.

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La Ciclosporina A (CsA) es un fármaco inmunosupresor que ha supuesto una revolución en el trasplante de órganos. A pesar de sus propiedades anti-inflamatorias, su uso se ha visto limitado por los efectos tóxicos que causa en algunos pacientes. La CsA inhibe la trascripción de genes involucrados en el sistema inmune. Se cree que esta inhibición es la causante de los efectos tóxicos producidos por el fármaco. El modo de acción de CsA está mediado por la unión de sus principales receptores intracelulares, las ciclofilinas (Cyps).

Las ciclofilinas son proteínas que están conservadas en todas las especies y su principal función está involucrada en el plegamiento correcto de otras proteínas. Se ha descrito que los efectos tóxicos producidos por CsA podían estar mediados directamente por sus receptores las ciclofilinas. A pesar de que se descrito que las ciclofilinas están involucradas en diferentes funciones, no se les atribuye una función específica.

En nuestro laboratorio hemos estado interesados en las posibles vías que involucran a las Cyps y si éstas tienen relación con lo efectos causados por CsA. En esta tesis se ha intentado identificar proteínas que interaccionan con CypA, CypB y FKBP12 y su implicación en los efectos tóxicos producidos por CsA.

Hemos identificado una serie de interacciones y hemos estudiado más a fondo dos de ellas. Estas interacciones son las ocurridas entre la ciclofilina B y la subunidad beta de la bomba sodio/potasio, la ciclofilina A y la subunidad beta de la bomba sodio/potasio y por último la ciclofilina B y la subunidad b1 de la ATP sintetasa mitocondrial. Una vez identificadas estas interacciones hemos realizado ensayos funcionales con cada una de ellas. Por un lado hemos estudiado si la actividad de la bomba sodio/potasio estaba afectada en células renales humanas tratadas con CsA y células que habían sido silenciadas para la ciclofilina B y ciclofilina A. Por otro lado hemos realizado un estudio de la actividad y expresión de los complejos de la cadena respiratoria mitocondrial en células renales tratadas con CsA y células renales que habían sido silenciadas para los genes CypA y CypB. A parte de las interacciones encontradas, hemos visto que la actividad de la bomba Na/K está disminuida por el fármaco y que en esta disminución estaría involucrada la ciclofilina B, también hemos visto que los complejos de la cadena respiratoria mitocondrial estarían afectados en células tratadas con CsA y en células interferidas tanto para CypB como para CypA.

Como conclusión podríamos sugerir que las ciclofilinas estarían involucradas en los efectos nefrotóxicos que produce la CsA. Estos efectos nefrotóxicos causados por el tratamiento con CsA podrían estar mediados por vias alternativas a la clásicamente descrita, como es la inhibición de la calcineurina. Dichas vías estarían integradas por nuevos efectores tales como Na/K-ATPasa, ATP sintetasa, así como otras putativas dianas que en el futuro serán estudiadas en nuestro laboratorio.
Cyclosporine A is an immunosuppressive drug that has revolutionized organ transplantation. Even though it has anti-inflammatory property, its used has been reduced due to the renal toxic effects caused in some patients. CsA inhibits transcription of genes involved in the immune system. The CsA mode of action involves the binding of its main receptors, the cyclophilins (Cyps).

Cyps are proteins conserved in all species and their main function is the correct folding of immature proteins. It has been describes that the main toxic effects caused by CsA could be mediated directly by its receptors, the cyclophilins. Although Cyps are involved in many processes, there is not a specific function for them.

In our lab, we have identified a number of proteins that interact with Cyclophilin A (CypA), Cyclophilin B (CypB) and FK-Binding Protein 12 (FKBP12) by yeast two hybrid assays. Some of those novel interactions were confirmed by pull-down and co-immunoprecipitation assays. Finally, we have also carried out functional assays in some of those interactions.

As a conclusion, we could suggest that cyclophilins would be involved in the nephrotoxic effects caused by cyclosporine A. Those effects are mediated by alternative pathways. Those pathways would be integrated by novel effectors such as the sodium/potassium ATPase, mitochondrial ATP synthase and also other proteins that will be studied in our lab.

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Georgiou, Charis. « Rational design of isoform specific ligands ». Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28713.

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Cyclophilins (Cyp) are proteins that catalyze the interconversion of trans/cis isomers of proline belonging to the peptidyl-prolyl isomerases family (PPIase). In addition to their PPIase activity, Cyps have diverse biological roles and have been implicated in a number of different diseases such as HIV-1 and HCV. Although several Cyp inhibitors have been reported in the literature, none are able to inhibit with high specificity various Cyp isoforms. To facilitate the development of isoform-specific Cyp ligands, we have pursued detailed studies of Cyp dynamics and ligand binding thermodynamics using molecular simulations, biophysical assays and protein X-ray crystallography. Research efforts were focussed on the identification of novel Cyp inhibitors using X-ray crystallographic studies and Surface Plasmon Resonance (SPR) experiments on fragments from an in-house bespoke library of small compounds. These biophysical studies revealed a number of fragments that are able to bind to diverse Cyp isoforms with high micromolar – low millimolar activity. To further examine the binding of these fragments to cyclophilins, identify interactions with the proteins and explain specificity trends from SPR and X-ray results, molecular dynamics (MD) simulations and free energy calculations were pursued. Models of apo and holo Cyps in complex with fragments that we had experimentally tested were set up using the Amber, AmberTools and FESetup software. Free energy calculations were performed using the thermodynamic integration (TI) technique with the Sire/OpenMM software. The results were analysed with custom scripts. Correlations between computed and measured binding energies, and calculated and observed binding modes were analysed to help develop guidelines for the development of isoform specific cyclophilin ligands. A detailed comparison of the merits and drawbacks of the experimental and computational techniques used in this work has also been made, and strategies for effective combination of the methodologies in structure-based projects are outlined.

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Norville, Isobel Harriet. « The identification and characterisation of PPIases from Burkholderia pseudomallei and Burkholderia thailandensis ». Thesis, University of Exeter, 2011. http://hdl.handle.net/10036/3152.

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The aim of this study was to identify and characterise peptidyl-prolyl cis-trans isomerases (PPIases) from the bacterium Burkholderia pseudomallei, the causative agent of the disease melioidosis. The longer term goal was to assess their potential as vaccine candidates or antimicrobial targets. Using bioinformatic approaches, six putative FK506-binding proteins (FKBPs) proteins and three putative parvulin proteins were identified in B. pseudomallei. Of these, six were expressed and purified as recombinant proteins. The purified proteins were used to immunise BALB/c mice, with some providing protection against a subsequent B. pseudomallei infection. These proteins could therefore be proposed as potential vaccine candidates. Homologues of Mip or SurA, which are associated with virulence in other bacterial species, were identified in B. pseudomallei and closely related B. thailandensis. Recombinant Mip or SurA homologues from B. pseudomallei were shown to have characteristic PPIase enzyme activity. To evaluate the role of the Mip homologue from B. pseudomallei in virulence, an unmarked deletion mutant was constructed. The mutant had reduced intracellular survival; defects in putative virulence mechanisms and attenuated virulence in mice. To assess the role of a SurA homologue, closely related B. thailandensis was used as a model organism, with deletion of the gene resulting in defects in intracellular infection, outer membrane integrity and virulence. This indicates that PPIases from B. pseudomallei and B. thailandensis represent novel virulence determinants and potential antimicrobial targets for therapeutics against melioidosis.

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Albasri, Hibah Mohammed. « Cell binding factor of Neisseria meningitidis is a PPIase with chaperone activity involved in outer membrane protein biogenesis ». Thesis, University of Nottingham, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.727113.

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Neisseria meningitidis is a major cause of meningitis and septicaemia which remain an important concern worldwide. Despite the advances in understanding the pathogenicity of N. meningitidis; its complexity is still not fully elucidated. Noteworthy, while a large number of complete genome sequences are now available, the annotation of each of the genes is incomplete with information either lacking entirely or based only on homology with genes in other species. In searching for novel genes in N. meningitidis strain MC58 that might be involved in the pathogenicity, a putative operon encoded by the genes NMB0342 to NMB0345 was bioinformatically identified and homology-based searches indicated that two of the genes, NMB0342 and NMB0345, have homologues in other pathogenic bacteria. This project was conducted to characterise the role of NMB0345 in meningococcal pathogenesis.

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Keogh, Rebecca. « Investigation of Peptidyl-prolyl cis/trans isomerases in the virulence of Staphylococcus aureus ». Ohio University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou158764341402963.

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Xu, Guoyan. « Pin1 Inhibitors : Towards Understanding the Enzymatic Mechanism ». Diss., Virginia Tech, 2010. http://hdl.handle.net/10919/37823.

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An important role of Pin1 is to catalyze the cis-trans isomerization of pSer/Thr-Pro bonds; as such, it plays an important role in many cellular events through the effects of conformational change on the function of its biological substrates, including Cdc25, c-Jun, and p53. The expression of Pin1 correlates with cyclin D1 levels, which contributes to cancer cell transformation. Overexpression of Pin1 promotes tumor growth, while its inhibition causes tumor cell apoptosis. Because Pin1 is overexpressed in many human cancer tissues, including breast, prostate, and lung cancer tissues, it plays an important role in oncogenesis, making its study vital for the development of anti-cancer agents. Many inhibitors have been discovered for Pin1, including 1) several classes of designed inhibitors such as alkene isosteres, non-peptidic, small molecular Pin1 inhibitors, and indanyl ketones, and 2) several natural products such as juglone, pepticinnamin E analogues, PiB and its derivatives obtained from a library screen. These Pin1 inhibitors show promise in the development of novel diagnostic and therapeutic anticancer drugs due to their ability to block cell cycle progression. In order to develop potent Pin1 inhibitors, the concept of transition-state analogues was used for the design of three classes of compounds: ketoamide, ketone, and reduced amide analogues. Specifically, a convergent synthesis of Î±-ketoamide inhibitors of Pin1 was developed. An Î±-hydroxyorthothioester derivative of Ser was reacted directly with an aminyl synthon. The reaction was catalyzed by HgO and HgCl2 to form an Î±-hydroxyamide. Hydrolysis and coupling were combined in one step in 80% yield. Two diastereomers of a phospho-Ser-Pro Î±-ketoamide analogue were synthesized. The resulting IC50 values of 100 ÂµM and 200 ÂµM were surprisingly weak for the Pin1 peptidyl-prolyl isomerase. Diastereomeric ketones were synthesized by coupling cyclohexenyl lithium to the serine Weinreb amide, via the Michael addition of a carboxylate synthon. The IC50 values of the two ketone diastereomers were determined to be 260 Î¼M and 61 Î¼M, respectively. Five reduced amide inhibitors for Pin1 were synthesized through a selective reduction using borane. The most potent inhibitor was found to be Fmocâ pSerâ Î¨[CH2N]-Proâ tryptamine, which had an IC50 value of 6.3 ÂµM. This represents a 4.5-fold better inhibition for Pin1 than a comparable cis-amide alkene isostere. The co-crystal structure of Acâ pSerâ Î¨[CH2N]-Proâ tryptamine bound to Pin1 was determined to 1.76 Ã resolution. Towards understanding the two proposed mechanisms of Pin1 catalysis, nucleophilic-additition mechanism and twisted-amide mechanism, three classes of Pin1 inhibitors (ketoamide, ketone, and reduced amide analogues) involving a total of nine compounds were synthesized and evaluated. The weak inhibitory activities of ketoamide and ketone analogues do not support the nucleophilic-addition mechanism, while the twisted-amide mechanism of Pin1 catalysis is promising based on the reduced amide inhibitors with good potencies.
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Mercedes-Camacho, Ana Yokayra. « Pin1 : WW domain ligands, catalytic inhibitors, and the mechanism ». Diss., Virginia Tech, 2011. http://hdl.handle.net/10919/77093.

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The peptidyl prolyl cis/trans isomerase, PPIase, has been the focus of numerous studies in the field of cell cycle regulation since proline-directed phosphorylation is an essential signaling mechanism that might arrest cancer proliferation. Pin1 is the first phosphorylation-dependent PPIase enzyme to be discovered. The Pin1 regulatory mechanism, acting on other mitotic proteins in vivo and in vitro, remains largely unknown. For the study of Pin1 function, two types of assays were used to identity ligands for Pin1: (1) The Enzyme-Linked Enzyme Binding Assay (ELEBA) for the identification of WW domain ligands, (2) a catalytic assay to identified inhibitors of Pin1 catalytic activity. The ELEBA offers a selective approach for detecting ligands that bind to the Pin1 WW domain from chemical libraries. By using the ELEBA, a pSer-Pro peptidomimetic library of 315 ligands was screened, identifying three promising ligands cis-D2, O2, and M18. Competitive Kd values for cis-D2, O2, and M18 were determined to be 263 ± 6.4, 206 ± 3.4, and 130 ± 3.0μM, respectively. Furthermore, we screened the pSer-Pro peptidomimetic library using a Pin1 discontinuous-catalytic assay to identify inhibitors of Pin1. Ligands D20 and K7 were identified to decrease more than 90% of the Pin1 catalytic activity. To investigate the nature of the Pin1 interaction with c-Myc, we synthesized and characterized four peptides corresponding to the c-Myc sequence. These peptides were used in NMR isomerization studies of Pin1 by our collaborator Dr. Jeffry Peng (University of Notre Dame). Preliminary work shows that Pin1 binds and isomerizes the Ac–LLPpTPPLSPS–NH₂ peptide at the cMyc pThr58 position. Finally, we measured a secondary kinetic isotope effect (2º KIE) to study the Pin1 catalytic mechanism of proline isomerization. The ratio of kH/kD for unlabeled and [d₃]Ser-labeled substrate gave a SKIE value of 1.34 ± 0.01. The normal 2º KIE value indicates that carbonyl-serine hybridization is not changing from sp² to sp³. This result supports substrate analogue inhibitor studies, and previous solvent and SKIE results on Pin1, that suggest a twisted amide mechanism assisted by a transient hydrogen bond in the transition state.
Ph. D.

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Brasseur, Anaïs. « Etude de composantes de la voie TOR : caractérisation de TbFKBP12, une protéine de la famille des PPIases (isomérases) impliquée dans l'homéostasie du flagelle chez Trypanosoma brucei ». Doctoral thesis, Universite Libre de Bruxelles, 2009. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210240.

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Trypanosoma brucei est un parasite africain unicellulaire, responsable chez l’homme de la maladie du sommeil et chez les bovins de la Nagana. Il passe par différents stades lors de son cycle de vie, les deux principaux étant la forme sanguicole qui prolifère dans le sang des mammifères infectés, et la forme procyclique qui colonise le tube digestif du vecteur, la mouche glossine.

Les trypanosomes sont extracellulaires, ils possèdent un flagelle qui leur permet de se mouvoir dans les différents milieux qu’ils infestent. La structure de celui-ci contient des éléments conservés au cours de l’évolution. Il constitue donc un excellent modèle de base pour en étudier l’architecture. D’autre part, le flagelle du parasite contient des structures propres à certains kinétoplastides, offrant ainsi une cible thérapeutique aux traitements anti-trypanosomiaux.

Le flagelle est véritablement un organite plurifonctionnel nécessaire à la survie du parasite au sein des divers environnements qu’il rencontre lors de son cycle de développement. Outre son rôle moteur, il permet à la cellule d’échapper au système immunitaire de son hôte mammifère et de s’attacher à l’épithélium des glandes salivaires de l’insecte. Il est également requis pour le bon positionnement des organites, la morphogenèse et la division cellulaire. Enfin, il serait impliqué dans l’activité sensorielle du trypanosome. A ce jour, on ne connait quasiment rien des potentielles voies de « sensing ». Elles doivent pourtant exister, permettant l’appréhension de l’environnement, l’interaction avec les hôtes et la réception de signaux induisant la différenciation.

Cet intérêt pour les voies de signalisation du parasite a abouti à l’étude des composantes de la voie TOR. TOR-Target of Rapamycin est un contrôleur central de la croissance cellulaire qu’il régule en fonction de différents stimuli externes. Il a été démontré depuis que chez T.brucei aussi, TOR régulerait la croissance temporelle et spatiale de la cellule.

La kinase TOR est inhibée par sa liaison avec le complexe rapamycine-FKBP12. Nous avons identifié cette peptidyl-prolyl cis-trans isomérase chez le parasite :TbFKBP12. Elle y serait localisée au niveau du cytosquelette/flagelle. Contrairement à ce qui est observé chez la levure S.cerevisiae, l’isomérase est essentielle chez le trypanosome. Son invalidation par RNAi bloque la cytocinèse des parasites sanguicoles et provoque l’apparition d’axes de clivage internes à la cellule. Chez les formes procycliques par contre, la disparition de la protéine entraîne un défaut sévère de motilité du flagelle qui se traduit par une immobilisation partielle du parasite.

TbFKBP12 est donc impliquée dans l’homéostasie du flagelle chez le trypanosome africain, organite nécessaire à la motilité et à la division cellulaire.

Doctorat en sciences, Spécialisation biologie moléculaire
info:eu-repo/semantics/nonPublished

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Rivas, Santos Pep. « Design and synthesis of engineered peptides to target undruggable PPIs : from in silico to in vitro studies ». Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/668150.

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Major unsolved diseases such as Cancer, cardiopathies or neurodegenerative disorders are frequently related with the malunction of complex protein networks. These networks are integrated by the interaction of multiple proteins that in case of a misregulation can trigger an undesired effect. Therefore, disruption of protein-protein interactions (PPIs), that are involucrated in a protein signalling cascade which is relevant for a particular diseases, is a hot topic in pharmaceutical industry. Unfortunately, traditional small molecules have been found to not be the most suitable inhibitiors of these therapeutic targets as PPI interfaces are characterized by a flat area with a lack of cavities that can fit a small molecule. In this scenario, peptides has called the attention in the drug discovery field for be a more appropiate candidates to target PPIs. Peptides are found in the chemical space between small molecules and antibodies, usullay contain between 2-50 amino acids and have an approximated weight of 250-10.000 Da. Then, their medium size allows a efficient recognition of the target protein without the need of well formed cavieties on the protein surface. However, peptides are characterized by a poor permeability and low stability in blood stream which had limited their therapeutic application in the past. Opportunately, introduction of non-natural amino acids and D-amino acids, N-alkylations of peptide backbone, cyclization and N-terminal and C-terminal modified cappings improve the biophysical properties along with the affinity for the receptor protein. Then, the use of engineered peptides, so-called peptidomimetics, is a promissing approach to target PPIs that can improve the binding potency of natural peptides and overcoming their major drawbacks at the same time. This thesis was carried out at Iproteos, a biotech company positioned in the use of peptidomimetics to target intracellular PPIs. The company has developed an in-house technology coined IPROTech, which is a platform that applys different in silico tools that are focused in the design of peptidomimetics, which are synthesized manually, quantified and finally evaluated in vitro. The experimental results are reintroduced in the platform and the process is repeated iteratively until achieve a final lead candidate. Hence, in the present work, IPROTech was applied to found de novo peptidomimetic molecules that inhibit the interaction of 4 different PPIs that are considered of therapeutic importance, Talin- Vinculin (Cancer), Rad51-BRCA2 (Cancer), Ras-Effectors (Cancer) and Retromer-L2 (HPVs infection). For each PPI, a collabration project with an academic group expert in field was setted up. Iproteos was in charge of the in silico studies of the target protein in order to design and synthesized a set peptidomimetic sequences that were predicted to disrupt the PPI of interest. On the other hand, the collaborators were responsible of the experimental evualtion of the synthesized compounds. In this terms, at least 1 hit was found for each PPI when evaluated in vitro, demonstrating an outsanding overall succes-rate of 31 % when all synthesized peptidomimetics were evaluated in vitro. Additinoally, the inclusion of new fancy builduing blocks into the compounds sintheysis, N-alkylation of the peptidomimetics backbone, pearmeability across biological barriers or the use of cyclodextrins as solvating excipient were other points studied as well.
Trobar nous fàrmacs capaços de trencar interaccions proteïna-proteïna, que d’alguna manera estan involucrades amb una malaltia, és de gran interès en el camp de la indústria farmacèutica. No obstant això, aquest tipus de diana terapèutica normalment no presenten cap cavitat ben definida a la seva superfície, característica necessària per albergar les tradicionals molècules petites. Per aquest motiu, la utilització de pèptids com a possibles fàrmacs és una aproximació molt prometedora perquè en tenir una mida molecular superior poden establir més interaccions amb la proteïna receptora afavorint així la seva unió. Però, aquesta aproximació està limitada per les propietats bioquímiques dels pèptids, ja que normalment són poc permeables i amb una baixa estabilitat un cop administrats. Afortunadament, els avanços fets en la síntesi de pèptids ha permès afegir modificacions sobre la seqüència dels pèptids per tal de millora les seves propietats, això inclou amino àcids no naturals, N-alquilacions, diferent tipus de N-terminals i C-terminals, entre altres. Els compostos obtinguts quan s’aplica aquesta enginyeria es coneixen com a peptidomimetics. Aquesta tesi es va realitzar a Iproteos. Iproteos és una petita empresa biotecnològica, focalitzada en l’ús de peptidomimetics per tal d’inhibir IPPs relacionades amb alguna malaltia. Per fer possible aquesta tasca, Iproteos ha creat una tecnologia, IPROTech, que agrupa tècniques computacionals per tal de cribrar la proteïna d’interès i genera estructures peptidometiques que més tard són sintetitzades, purificades i quantificades. Per aquesta tesi, es va aplicar la tecnologia IPROTech per trobar peptidomimetics amb la capacitat d’inhibir quatre IPP de rellevància terapèutica, Talina-Vinculina (càncer), Rad51- BRCA2 (càncer), Ras-Effectors (càncer) i Retromer-L2 (HPVs). Per cadascuna d’aquestes dianes, a Iproteos es va realitzar els estudis in silico i la síntesi dels peptidomimetics mentre que l'avaluació experimental la van fer grups acadèmics experts en cada camp. En tots els casos es va trobar almenys un compost capaç de trencar amb la interacció. Addicionalment propietats com la solubilitat, permeabilitat o estabilitat van ser avaluades per aquells compostos actius. Finalment, gràcies a les dades generades, alguns d’aquests compostos es van poder optimitzar obtenint un candidat final més potent encara.

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Ruiz-Gómez, Gloria, John C. Hawkins, Jenny Philipp, Georg Künze, Robert Wodtke, Reik Löser, Karim Fahmy et M. Teresa Pisabarro. « Rational Structure-Based Rescaffolding Approach to De Novo Design of Interleukin 10 (IL-10) Receptor-1 Mimetics ». Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-215877.

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Tackling protein interfaces with small molecules capable of modulating protein-protein interactions remains a challenge in structure-based ligand design. Particularly arduous are cases in which the epitopes involved in molecular recognition have a non-structured and discontinuous nature. Here, the basic strategy of translating continuous binding epitopes into mimetic scaffolds cannot be applied, and other innovative approaches are therefore required. We present a structure-based rational approach involving the use of a regular expression syntax inspired in the well established PROSITE to define minimal descriptors of geometric and functional constraints signifying relevant functionalities for recognition in protein interfaces of non-continuous and unstructured nature. These descriptors feed a search engine that explores the currently available three-dimensional chemical space of the Protein Data Bank (PDB) in order to identify in a straightforward manner regular architectures containing the desired functionalities, which could be used as templates to guide the rational design of small natural-like scaffolds mimicking the targeted recognition site. The application of this rescaffolding strategy to the discovery of natural scaffolds incorporating a selection of functionalities of interleukin-10 receptor-1 (IL-10R1), which are relevant for its interaction with interleukin-10 (IL-10) has resulted in the de novo design of a new class of potent IL-10 peptidomimetic ligands.

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Livres sur le sujet "PPIasa"

Hallim Taehakkyo (Korea). Asia Munhwa Yŏn'guso. Han'guk chŏnjaenggi ppira. Kangwŏn-do Ch'unch'ŏn-si : Institute of Asian Culture Studies Hallym University, 2000.

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Munhwagwan, Ch'ŏnggyech'ŏn. Poiji annŭn chŏnjaeng, ppira : Propaganda leaflets. Sŏul T'ŭkpyŏlsi : Ch'ŏnggyech'ŏn Munhwagwan, 2010.

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Chŏk ŭl ppira ro mudŏra : Han'guk Chŏnjaenggi Miguk ŭi simnijŏn. Sŏul : Ch'ŏlsu wa Yŏnghŭi, 2012.

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Han'guk Chŏnjaeng kwa si, kun'ga, ppira : Han'guk Chŏnjaeng palbal 60-chunyŏn. Sŏul : Hwanam, 2010.

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Ppira esŏ tidosŭ kkaji : Pukhan taenam saibŏ t'erŏ ŭi hyŏnjae wa mirae. Sŏul-si : Kŭlt'ong, 2013.

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Champsaur, Paul. Les indices de prix de vente de l'industrie et des services aux entreprises [PVIS] : The French producer price indices and business-service price indices [PPIs]. Paris : INSEE, 1999.

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Hallim Taehakkyo (Korea). Asia Munhwa Yŏnʾguso., dir. Hanʾguk chŏnjaenggi ppira. Sŏul-si : Institute of Asian culture studies Hallym University, 2000.

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Sawada, Osamu. Minimizer PPIs. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780198714224.003.0005.

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Chapter 5 investigates the varieties of minimizers in Japanese (and other languages) and considers the source of variations from a semantics/pragmatics interface. Although sukoshi and chotto denote a small degree, they are different in terms of granularity: sukoshi conventionally implies that a speaker is measuring degrees with a scale that is precise, whereas chotto conventionally implies that the speaker is measuring degrees imprecisely. This difference naturally explains why chotto and not sukoshi has a speech act use. The speech act minimizer measures the degree of imposition of a speech act on the hearer, and the degree of imposition is something that cannot be measured precisely. This chapter shows that the not-at-issue component of minimizers plays an important role in explaining the varieties of minimizers.

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Jacques Ppins New Complete Techniques. Black Dog & Leventhal Publishers, 2012.

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Rashid, Nuraisyah Mohamed, et Persatuan Pemudi Islam Singapura, dir. Lighting lives : The PPIS story. Singapore : Persatuan Pemudi Islam Singapura, 2008.

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Chapitres de livres sur le sujet "PPIasa"

Antoniou, Giannakis, Campbell Wilson et Dimitris Geneiatakis. « PPINA – A Forensic Investigation Protocol for Privacy Enhancing Technologies ». Dans Communications and Multimedia Security, 185–95. Berlin, Heidelberg : Springer Berlin Heidelberg, 2006. http://dx.doi.org/10.1007/11909033_17.

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Kurek, I., N. Erel, C. Mayr, E. Herman et A. Breiman. « Novel Wheat Molecular Chaperones Belonging to the PPIase-FKBP Family : Studies on Their Regulation and Tissue Specificity ». Dans Plant Biotechnology and In Vitro Biology in the 21st Century, 417–20. Dordrecht : Springer Netherlands, 1999. http://dx.doi.org/10.1007/978-94-011-4661-6_93.

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Pandey, Saurabh, Javeed Ahmad et Nasreen Zafar Ehtesham. « Chaperone-Like Proteins in Inflammation and Immunomodulation : Examples of Resistin and PPIases ». Dans Heat Shock Proteins, 179–91. Cham : Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-02254-9_9.

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Ni, Duan, Na Liu et Chunquan Sheng. « Allosteric Modulators of Protein–Protein Interactions (PPIs) ». Dans Advances in Experimental Medicine and Biology, 313–34. Singapore : Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-8719-7_13.

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Poluri, Krishna Mohan, Khushboo Gulati et Sharanya Sarkar. « Energetic Aspects of Protein–Protein Interactions (PPIs) ». Dans Protein-Protein Interactions, 113–51. Singapore : Springer Singapore, 2021. http://dx.doi.org/10.1007/978-981-16-1594-8_3.

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He, Houhua, Lei Yu, Weixia Cai, Xiaoyu Wang, Xiaorui Gong, Haoyu Wang et Chen Liu. « PPIDS : A Pyramid-Like Printer Intrusion Detection System Based on ATT&CK Framework ». Dans Information Security and Cryptology, 277–90. Cham : Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-42921-8_16.

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Lin, Xiaoli, QianQian Huang et Fengli Zhou. « Effective Identification of Hot Spots in PPIs Based on Ensemble Learning ». Dans Intelligent Computing Theories and Application, 199–207. Cham : Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-63312-1_18.

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García-Echeverría, Carlos, James L. Kofron, Petr Kuzmic, Vimal Kishore et Daniel H. Rich. « Intramolecularly quenched fluorescent peptide substrates of peptidyl-prolyl cis-trans isomerases : The first direct fluorimetric assay for PPIases ». Dans Peptides 1992, 479–80. Dordrecht : Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1470-7_212.

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Schauer, K., et K. Stingl. « ‘Guilty by Association&rsquo ; &ndash ; Protein-Protein Interactions (PPIs) in Bacterial Pathogens ». Dans Microbial Pathogenomics, 48–61. Basel : KARGER, 2009. http://dx.doi.org/10.1159/000235762.

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Wetie, Armand G. Ngounou, Alisa G. Woods et Costel C. Darie. « Mass Spectrometric Analysis of Post-translational Modifications (PTMs) and Protein–Protein Interactions (PPIs) ». Dans Advances in Experimental Medicine and Biology, 205–35. Cham : Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-06068-2_9.

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Actes de conférences sur le sujet "PPIasa"

« PPiTTA - Preserving Privacy in TV Targeted Advertising ». Dans International Conference on Security and Cryptography. SciTePress - Science and and Technology Publications, 2012. http://dx.doi.org/10.5220/0004076103270332.

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Suminar, Suryo, et Fitroh dan Suci Ratnawati. « Evaluation of information technology governance using COBIT 5 framework focus AP013 and DSS05 in PPIKSN-BATAN ». Dans 2014 International Conference on Cyber and IT Service Management (CITSM). IEEE, 2014. http://dx.doi.org/10.1109/citsm.2014.7042166.

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Gasperin, Matej, Vladimir Jovan et Dejan Gradisar. « Decision support system for polymerization production plant using pPIs ». Dans Automation (MED 2008). IEEE, 2008. http://dx.doi.org/10.1109/med.2008.4602130.

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Zhang, Wenfeng, Congfa Huang et Haixiao Zou. « Abstract 2134 : Cyclosporin-A enhances cisplatin induced-apoptosis through inhibition PPIase activity of cyclophinlin A and Akt signaling pathway in a human tongue squamous cell carcinoma ». Dans Proceedings : AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011 ; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-2134.

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Bett, Dominic K., et Ananda Mohan Mondal. « Diffusion kernel to identify missing PPIs in protein network biomarker ». Dans 2015 IEEE International Conference on Bioinformatics and Biomedicine (BIBM). IEEE, 2015. http://dx.doi.org/10.1109/bibm.2015.7359917.

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Pal, Debasmita, Anindita Sarkar Mondal et Kartick Chandra Mondal. « Knowledge discovery from HIV-1-human PPIs assimilating interaction keywords ». Dans 2016 International Conference on Computer, Electrical & Communication Engineering (ICCECE). IEEE, 2016. http://dx.doi.org/10.1109/iccece.2016.8009568.

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Santos, Maria, Elizabeth Lopes, Margarida Espadinha, Mattia Mori et Maurizio Botta. « Enhancing anticancer activity of spiropyrazoline oxindoles by disrupting p53-MDMs PPIs ». Dans 5th International Electronic Conference on Medicinal Chemistry. Basel, Switzerland : MDPI, 2019. http://dx.doi.org/10.3390/ecmc2019-06352.

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Pena, Francisco I., et Young-Rae Cho. « Improvements of graph entropy approach to detect protein complexes by ontological analysis of PPIs ». Dans 2012 IEEE International Conference on Bioinformatics and Biomedicine Workshops (BIBMW). IEEE, 2012. http://dx.doi.org/10.1109/bibmw.2012.6470306.

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Ray, Sumanta, Anirban Mukhopadhyay et Ujjawal Maulik. « Predicting annotated HIV-1-Human PPIs using a biclustering approach to association rule mining ». Dans 2012 Third International Conference on Emerging Applications of Information Technology (EAIT). IEEE, 2012. http://dx.doi.org/10.1109/eait.2012.6407854.

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Heru, Atmanto, Silami Dwi, Ryan Crysandi, Ninis Makhnunah, Budi Purnama, Ari H. Ramelan et Henning Storz. « The Development of Polypropylene Itaconate (PPIA) for the Film Sensor as Preliminary Study for Meat Distinguisher ». Dans 2014 International Conference on Physics and its Applications. Paris, France : Atlantis Press, 2015. http://dx.doi.org/10.2991/icopia-14.2015.14.

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Rapports d'organisations sur le sujet "PPIasa"

Izquierdo, Alejandro, Jimena Llopis, Umberto Muratori et José Juan Ruiz. Priorities for Productivity and Income (PPIs) : Country Results : Peru. Inter-American Development Bank, août 2015. http://dx.doi.org/10.18235/0000085.

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Izquierdo, Alejandro, Jimena Llopis, Umberto Muratori et José Juan Ruiz. Priorities for Productivity and Income (PPIs) : Country Results : Bolivia. Inter-American Development Bank, août 2015. http://dx.doi.org/10.18235/0000088.

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Izquierdo, Alejandro, Jimena Llopis, Umberto Muratori et José Juan Ruiz. Priorities for Productivity and Income (PPIs) : Country Results : Argentina. Inter-American Development Bank, août 2015. http://dx.doi.org/10.18235/0000089.

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Tong, Yaliang, Shaoyou Qin, Zhenting Wu, Yuquan He, Changyu Zhou et Ping Yang. The efficacy and safety of proton pump inhibitors (PPIs) for the prevention of antiplatelet drug-associated peptic ulcers or gastrointestinal hemorrhage : A systematic review and meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, décembre 2020. http://dx.doi.org/10.37766/inplasy2020.12.0078.

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