Contents
Academic literature on the topic 'Protein–protein interaction metabolon substrate channeling'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Protein–protein interaction metabolon substrate channeling.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "Protein–protein interaction metabolon substrate channeling"
1
Sastre, Diego E., André A. Pulschen, Luis G. M. Basso, et al. "The phosphatidic acid pathway enzyme PlsX plays both catalytic and channeling roles in bacterial phospholipid synthesis." Journal of Biological Chemistry 295, no. 7 (2020): 2148–59. http://dx.doi.org/10.1074/jbc.ra119.011147.
Full textAbstract:
PlsX is the first enzyme in the pathway that produces phosphatidic acid in Gram-positive bacteria. It makes acylphosphate from acyl-acyl carrier protein (acyl-ACP) and is also involved in coordinating phospholipid and fatty acid biosyntheses. PlsX is a peripheral membrane enzyme in Bacillus subtilis, but how it associates with the membrane remains largely unknown. In the present study, using fluorescence microscopy, liposome sedimentation, differential scanning calorimetry, and acyltransferase assays, we determined that PlsX binds directly to lipid bilayers and identified its membrane anchoring moiety, consisting of a hydrophobic loop located at the tip of two amphipathic dimerization helices. To establish the role of the membrane association of PlsX in acylphosphate synthesis and in the flux through the phosphatidic acid pathway, we then created mutations and gene fusions that prevent PlsX's interaction with the membrane. Interestingly, phospholipid synthesis was severely hampered in cells in which PlsX was detached from the membrane, and results from metabolic labeling indicated that these cells accumulated free fatty acids. Because the same mutations did not affect PlsX transacylase activity, we conclude that membrane association is required for the proper delivery of PlsX's product to PlsY, the next enzyme in the phosphatidic acid pathway. We conclude that PlsX plays a dual role in phospholipid synthesis, acting both as a catalyst and as a chaperone protein that mediates substrate channeling into the pathway.
2
Xia, Chuanwu, Zhuji Fu, Kevin P. Battaile та Jung-Ja P. Kim. "Crystal structure of human mitochondrial trifunctional protein, a fatty acid β-oxidation metabolon". Proceedings of the National Academy of Sciences 116, № 13 (2019): 6069–74. http://dx.doi.org/10.1073/pnas.1816317116.
Full textAbstract:
Membrane-bound mitochondrial trifunctional protein (TFP) catalyzes β-oxidation of long chain fatty acyl-CoAs, employing 2-enoyl-CoA hydratase (ECH), 3-hydroxyl-CoA dehydrogenase (HAD), and 3-ketothiolase (KT) activities consecutively. Inherited deficiency of TFP is a recessive genetic disease, manifesting in hypoketotic hypoglycemia, cardiomyopathy, and sudden death. We have determined the crystal structure of human TFP at 3.6-Å resolution. The biological unit of the protein is α2β2. The overall structure of the heterotetramer is the same as that observed by cryo-EM methods. The two β-subunits make a tightly bound homodimer at the center, and two α-subunits are bound to each side of the β2dimer, creating an arc, which binds on its concave side to the mitochondrial innermembrane. The catalytic residues in all three active sites are arranged similarly to those of the corresponding, soluble monofunctional enzymes. A structure-based, substrate channeling pathway from the ECH active site to the HAD and KT sites is proposed. The passage from the ECH site to the HAD site is similar to those found in the two bacterial TFPs. However, the passage from the HAD site to the KT site is unique in that the acyl-CoA intermediate can be transferred between the two sites by passing along the mitochondrial inner membrane using the hydrophobic nature of the acyl chain. The 3′-AMP-PPi moiety is guided by the positively charged residues located along the “ceiling” of the channel, suggesting that membrane integrity is an essential part of the channel and is required for the activity of the enzyme.
3
Crawford, Russell M., Kate J. Treharne, Sandrine Arnaud-Dabernat та ін. "Understanding the Molecular Basis of the Interaction between NDPK-A and AMPK α1". Molecular and Cellular Biology 26, № 15 (2006): 5921–31. http://dx.doi.org/10.1128/mcb.00315-06.
Full textAbstract:
ABSTRACT Nucleoside diphosphate kinase (NDPK) (nm23/awd) belongs to a multifunctional family of highly conserved proteins (∼16 to 20 kDa) including two well-characterized isoforms (NDPK-A and -B). NDPK catalyzes the conversion of nucleoside diphosphates to nucleoside triphosphates, regulates a diverse array of cellular events, and can act as a protein histidine kinase. AMP-activated protein kinase (AMPK) is a heterotrimeric protein complex that responds to the cellular energy status by switching off ATP-consuming pathways and switching on ATP-generating pathways when ATP is limiting. AMPK was first discovered as an activity that inhibited preparations of acetyl coenzyme A carboxylase 1 (ACC1), a regulator of cellular fatty acid synthesis. We recently reported that NDPK-A (but not NDPK-B) selectively regulates the α1 isoform of AMPK independently of the AMP concentration such that the manipulation of NDPK-A nucleotide trans-phosphorylation activity to generate ATP enhanced the activity of AMPK. This regulation occurred irrespective of the surrounding ATP concentration, suggesting that “substrate channeling” was occurring with the shielding of NDPK-generated ATP from the surrounding medium. We speculated that AMPK α1 phosphorylated NDPK-A during their interaction, and here, we identify two residues on NDPK-A targeted by AMPK α1 in vivo. We find that NDPK-A S122 and S144 are phosphorylated by AMPK α1 and that the phosphorylation status of S122, but not S144, determines whether substrate channeling can occur. We report the cellular effects of the S122 mutation on ACC1 phosphorylation and demonstrate that the presence of E124 (absent in NDPK-B) is necessary and sufficient to permit both AMPK α1 binding and substrate channeling.
4
Youjun, Zhang, and R. Fernie Alisdair. "Metabolons, enzyme–enzyme assemblies that mediate substrate channeling, and their roles in plant metabolism." June 5, 2020. https://doi.org/10.1016/j.xplc.2020.100081.
Full textAbstract:
Metabolons are transient multi-protein complexes of sequential enzymes that mediate substrate channeling. They differ from multi-enzyme complexes in that they are dynamic, rather than permanent, and as such have considerably lower dissociation constants. Despite the fact that a huge number of metabolons have been suggested to exist in plants, most of these claims are erroneous as only a handful of these have been proven to channel metabolites. We believe that physical protein–protein interactions between consecutive enzymes of a pathway should rather be called enzyme–enzyme assemblies. In this review, we describe how metabolons are generally assembled by transient interactions and held together by both structural elements and non-covalent interactions. Experimental evidence for their existence comes from protein–protein interaction studies, which indicate that the enzymes physically interact, and direct substrate channeling measurements, which indicate that they functionally interact. Unfortunately, advances in cell biology and proteomics have far outstripped those in classical enzymology and flux measurements, rendering most reports reliant purely on interactome studies. Recent developments in co-fractionation mass spectrometry will likely further exacerbate this bias. Given this, only dynamic enzyme–enzyme assemblies in which both physical and functional interactions have been demonstrated should be termed metabolons. We discuss the level of evidence for the manifold plant pathways that have been postulated to contain metabolons and then list examples in both primary and secondary metabolism for which strong evidence has been provided to support these claims. In doing so, we pay particular attention to experimental and mathematical approaches to study metabolons as well as complexities that arise in attempting to follow them. Finally, we discuss perspectives for improving our understanding of these fascinating but enigmatic interactions.
5
Omini, Joy, Taiwo Dele-Osibanjo, Heejeong Kim, Jing Zhang, and Toshihiro Obata. "Is the TCA cycle malate dehydrogenase-citrate synthase metabolon an illusion?" Essays in Biochemistry, July 3, 2024. http://dx.doi.org/10.1042/ebc20230084.
Full textAbstract:
Abstract This review discusses the intriguing yet controversial concept of metabolons, focusing on the malate dehydrogenase-citrate synthase (MDH-CISY) metabolon as a model. Metabolons are multienzyme complexes composed of enzymes that catalyze sequential reactions in metabolic pathways. Metabolons have been proposed to enhance metabolic pathway efficiency by facilitating substrate channeling. However, there is skepticism about the presence of metabolons and their functionality in physiological conditions in vivo. We address the skepticism by reviewing compelling evidence supporting the existence of the MDH-CISY metabolon and highlighting its potential functions in cellular metabolism. The electrostatic interaction between MDH and CISY and the intermediate oxaloacetate, channeled within the metabolon, has been demonstrated using various experimental techniques, including protein–protein interaction assays, isotope dilution studies, and enzyme coupling assays. Regardless of the wealth of in vitro evidence, further validation is required to elucidate the functionality of MDH-CISY metabolons in living systems using advanced structural and spatial analysis techniques.
6
Youjun, Zhang, and R. Fernie Alisdair. "Stable and temporary enzyme complexes and metabolons involved in energy and redox metabolism." December 28, 2020. https://doi.org/10.1089/ars.2019.7981.
Full textAbstract:
<strong><em>Significance:</em></strong> Alongside well-characterized permanent multimeric enzymes and multienzyme complexes, relatively unstable transient enzyme–enzyme assemblies, including metabolons, provide an important mechanism for the regulation of energy and redox metabolism. <strong><em>Critical Issues:</em></strong> Despite the fact that enzyme–enzyme assemblies have been proposed for many decades and experimentally analyzed for at least 40 years, there are very few pathways for which unequivocal evidence for the presence of metabolite channeling, the most frequently evoked reason for their formation, has been provided. Further, in contrast to the stronger, permanent interactions for which a deep understanding of the subunit interface exists, the mechanism(s) underlying transient enzyme–enzyme interactions remain poorly studied. <strong><em>Recent Advances:</em></strong> The widespread adoption of proteomic and cell biological approaches to characterize protein–protein interaction is defining an ever-increasing number of enzyme–enzyme assemblies as well as enzyme–protein interactions that likely identify factors which stabilize such complexes. Moreover, the use of microfluidic technologies provided compelling support of a role for substrate-specific chemotaxis in complex assemblies. <strong><em>Future Directions:</em></strong> Embracing current and developing technologies should render the delineation of metabolons from other enzyme–enzyme complexes more facile. In parallel, attempts to confirm that the findings reported in microfluidic systems are, indeed, representative of the cellular situation will be critical to understanding the physiological circumstances requiring and evoking dynamic changes in the levels of the various transient enzyme–enzyme assemblies of the cell.
7
Zhang, Youjun, Arun Sampathkumar, Sandra Mae-Lin Kerber, et al. "A moonlighting role for enzymes of glycolysis in the co-localization of mitochondria and chloroplasts." Nature Communications 11, no. 1 (2020). http://dx.doi.org/10.1038/s41467-020-18234-w.
Full textAbstract:
Abstract Glycolysis is one of the primordial pathways of metabolism, playing a pivotal role in energy metabolism and biosynthesis. Glycolytic enzymes are known to form transient multi-enzyme assemblies. Here we examine the wider protein-protein interactions of plant glycolytic enzymes and reveal a moonlighting role for specific glycolytic enzymes in mediating the co-localization of mitochondria and chloroplasts. Knockout mutation of phosphoglycerate mutase or enolase resulted in a significantly reduced association of the two organelles. We provide evidence that phosphoglycerate mutase and enolase form a substrate-channelling metabolon which is part of a larger complex of proteins including pyruvate kinase. These results alongside a range of genetic complementation experiments are discussed in the context of our current understanding of chloroplast-mitochondrial interactions within photosynthetic eukaryotes.
8
Youjun, Zhang, Sampathkumar Arun, Mae-Lin Kerber Sandra, et al. "A moonlighting role for enzymes of glycolysis in the co-localization of mitochondria and chloroplasts." September 9, 2020. https://doi.org/10.1038/s41467-020-18234-w.
Full textAbstract:
Glycolysis is one of the primordial pathways of metabolism, playing a pivotal role in energy metabolism and biosynthesis. Glycolytic enzymes are known to form transient multi-enzyme assemblies. Here we examine the wider protein-protein interactions of plant glycolytic enzymes and reveal a moonlighting role for specific glycolytic enzymes in mediating the co-localization of mitochondria and chloroplasts. Knockout mutation of phosphoglycerate mutase or enolase resulted in a significantly reduced association of the two organelles. We provide evidence that phosphoglycerate mutase and enolase form a substrate-channelling metabolon which is part of a larger complex of proteins including pyruvate kinase. These results alongside a range of genetic complementation experiments are discussed in the context of our current understanding of chloroplast-mitochondrial interactions within photosynthetic eukaryotes.
9
Zamarreño, Beas Jordi, Marco A.M. Videira, and Ligia M. Saraiva. "Regulation of bacterial haem biosynthesis." February 1, 2022. https://doi.org/10.1016/j.ccr.2021.2142.
Full textAbstract:
Haem <em>b</em> and sirohaem are two iron-chelated modified tetrapyrroles that serve as prosthetic groups in proteins with crucial roles in a variety of biological functions, such as gas transport, respiration, and nitrite and sulphite reduction. These tetrapyrroles are synthesised from 5-aminolaevulinic acid and share a common pathway until the formation of uroporphyrinogen III, from where the synthesis diverges. In bacteria, sirohaem is produced from uroporphyrinogen III through the activities of one, two or three separate proteins, while haem <em>b</em> is synthesised through three distinct pathways. The biosynthesis of haem <em>b</em> and sirohaem comprises intermediates and end-products that are unstable or potentially hazardous to the cell. Therefore, the cellular metabolic fluxes of tetrapyrroles need to be tightly controlled by substrate channelling and/or other regulatory processes. This review summarises the recent advances on the regulation and protein–protein interactions controlling the formation of sirohaem and haem <em>b</em> in bacteria.
10
Rivero, Maribel, Sergio Boneta, Nerea Novo, Adrián Velázquez-Campoy, Victor Polo, and Milagros Medina. "Riboflavin kinase and pyridoxine 5′-phosphate oxidase complex formation envisages transient interactions for FMN cofactor delivery." Frontiers in Molecular Biosciences 10 (March 28, 2023). http://dx.doi.org/10.3389/fmolb.2023.1167348.
Full textAbstract:
Enzymes catalysing sequential reactions have developed different mechanisms to control the transport and flux of reactants and intermediates along metabolic pathways, which usually involve direct transfer of metabolites from an enzyme to the next one in a cascade reaction. Despite the fact that metabolite or substrate channelling has been widely studied for reactant molecules, such information is seldom available for cofactors in general, and for flavins in particular. Flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) act as cofactors in flavoproteins and flavoenzymes involved in a wide range of physiologically relevant processes in all type of organisms. Homo sapiens riboflavin kinase (RFK) catalyses the biosynthesis of the flavin mononucleotide cofactor, and might directly interplay with its flavin client apo-proteins prior to the cofactor transfer. Non-etheless, none of such complexes has been characterized at molecular or atomic level so far. Here, we particularly evaluate the interaction of riboflavin kinase with one of its potential FMN clients, pyridoxine-5′-phosphate oxidase (PNPOx). The interaction capacity of both proteins is assessed by using isothermal titration calorimetry, a methodology that allows to determine dissociation constants for interaction in the micromolar range (in agreement with the expected transient nature of the interaction). Moreover, we show that; i) both proteins become thermally stabilized upon mutual interaction, ii) the tightly bound FMN product can be transferred from RFK to the apo-form of PNPOx producing an efficient enzyme, and iii) the presence of the apo-form of PNPOx slightly enhances RFK catalytic efficiency. Finally, we also show a computational study to predict likely RFK-PNPOx binding modes that can envisage coupling between the FMN binding cavities of both proteins for the potential transfer of FMN.
Book chapters on the topic "Protein–protein interaction metabolon substrate channeling"
1
Prabhakaran, Pranesha, Yusuf Nazir, Hafiy Halim, Aidil Abdul Hamid, and Yuanda Song. "Multienzyme Complex in Fatty Acid Biosynthesis." In Fungal Lipid Biochemistry. BENTHAM SCIENCE PUBLISHERS, 2023. http://dx.doi.org/10.2174/9789815123012123010007.
Full textAbstract:
Fatty acid biosynthesis is a fundamental process that occurs in all living organisms and involves multiple reaction steps. Thus, a systematic transfer of the intermediates between the different catalytic sites is highly required for the efficient regulation of a pathway as well as for sustaining growth. Multienzyme complex, a protein complex that comprises a group of interacting enzymes in a specific metabolic pathway, has been identified to catalyze numerous metabolic pathways, including fatty acid synthesis. The existence of a lipogenic multienzyme complex that involves protein interaction between numerous enzymes that took part in fatty acid biosynthesis plays a key fundamental role in channelling the intermediate substrates. Herein, the growing evidence for the formation of multienzyme complexes in fatty acid synthesis and the properties of the complex will be elucidated in this chapter.