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phosphoglycerate mutase function

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Several features of Rigden DJ, Walter RA, Phillips SE, Fothergill-Gilmore LA. doi:10.1038/s41418-017-0034-y, 16. doi:10.1016/j.cmet.2019.09.014. 50. Phosphoglycerate mutase helps carry out a chemical reaction that converts a molecule called 3-phosphoglycerate, which is produced during the breakdown of glucose, to another molecule called 2 … The promoting role of PGAM1 on tumor metastasis has also been unveiled, but rarely related to the glycolytic functions of PGAM1. 30. Mol Cancer. doi:10.1016/j.cell.2011.02.013, 4. Zhang D, Wu H, Zhang X, et al. 229, 383-7, (1988). (A) The 3D structure of PGAM1 from SWISS-MODEL website (https://swissmodel.expasy.org/docs/terms_of_use). 2009;136(3):521–534. Such information will provide novel concepts for future investigation of PGAM1 as a potential target for cancer therapy. Shanske S, Sakoda S, Hermodson MA, DiMauro S, Schon EA. -. Table 1 Effects of Different Inhibitors of PGAM1 on Proliferation and Metastasis of Various Cancer. eCollection 2020. 2010;185:649–662. Overview. doi:10.1039/b705113a, 22. -, Andriotis VM, Kruger NJ, Pike MJ, Smith AM. 2008;32(10):1215–1222. Stanford, CA: Stanford Unversity Press; 1987. pp. (A) iPGAM1 and…, NLM doi:10.1038/onc.2016.446, 24. Dr. Li was involved in the conception and design, the first draft of the article, final approval of the article, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved. PGAM1 belongs to the phosphoglycerate mutase family, which can be subdivided into monophosphoglycerate mutases (mPGAM) and bisphosphoglycerate mutases (BPGAM). Nucleic Acids Research. Figure 2 Schematic diagram showing the current understanding of the role of PGAM1 in cancer cells and the research directions of PGAM1-targeted drugs. doi:10.1016/j.bbcan.2012.12.004, 11. Since PGAM1 was suggested as a potential therapeutic target for multiple cancer types, several PGAM1 inhibitors have been developed for cancer therapy.21,22,28,50–53 A summary of these inhibitors and their related functions are listed in Table 1. Bisphosphoglycerate mutase (BPGM) is an enzyme unique to erythrocytes and placental cells. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. Mol Cancer. Oncol Res. Although there are many unsolved questions around the roles of PGAM1 in tumor malignant behaviors, increasing evidence suggests that it has become an emerging and promising target for cancer therapy and worth further investigation in the future. 2018;26(8):1961–1970. Extracellular nucleotides and apyrases regulate stomatal aperture in Arabidopsis. This method for ATP production is known as substrate-level phosphorylation because it produces energy storing ATP molecules withou… Xu Z, Gong J, Wang C, et al. 58. Xanthone derivatives as phosphoglycerate mutase 1 inhibitors: design, synthesis, and biological evaluation. Tyr26 phosphorylation of PGAM1 provides a metabolic advantage to tumours by stabilizing the active conformation. It is responsible for the catalytic synthesis of 2,3-Bisphosphoglycerate (2,3-BPG) from 1,3-bisphosphoglycerate. Jacobowitz DM, Jozwik C, Fukuda T, Pollard HB. FEBS Lett. Cofactor-dependent phosphoglycerate mutase exists as a homodimer composed of alpha/beta subunits with a t wo-fold symmetry about the central core. Copyright 2017 Informa PLC. 2014 Feb;55(2):241-50. doi: 10.1093/pcp/pct145. Phosphoglycerate mutase is an enzyme that has an very important role in human biochemistry and across many different taxa. Phosphoglycerate mutase is involved in a critical energy-producing process known as glycolysis. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms. Would you like email updates of new search results? Finally, Liu et al.36 found that the overexpression of PGAM1 correlated with poor prognosis in PDAC patients after analyzing 54 PDAC clinical tissues. Proc Natl Acad Sci U S A. It derives from a glyceric acid. Cell. doi: 10.7717/peerj.9107. Xu Q, Tu J, Dou C, et al. The latter has been associated with the non-glycolytic function of PGAM1. doi:10.3892/or.2016.5046, 21. doi:10.1126/science.123.3191.309, 2. On the origin of cancer cells. 1989;62:227–313. Surprisingly, in the latest study by Huang et al.56 reported the first allosteric PGAM1 inhibitor HKB99, which suppresses NSCLC tumor growth through ROS-dependent activation of JNK/c-Jun and metastasis by abrogating the interaction between PGAM1 and ACTA2. On the other hand, PGAM1 can promote cancer cell invasion and metastasis through a specific non-glycolytic function. Shackelford DB, Shaw RJ. 2020 Jun 29;8:e9107. On respiratory impairment in cancer cells. Vegetative plant growth was severely impaired in the double mutants and pollen was not produced. 2011;144(5):646–674. Evans MJ, Morris GM, Wu J, Olson AJ, Sorensen EJ, Cravatt BF. Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. The expression of PGAM1 was higher in tumor tissues than in adjacent normal tissues.24–27 Altogether, these findings indicate that PGAM1 could be a potential target for cancer therapy. However, most of the PGAM1 inhibitors were glycolysis-targeted with minimal to no effect on the invasion and metastasis of cancer cells (Table 1). In this study, PGAM1 was found to directly interact with α-smooth muscle actin 2 (ACTA2) independent of its metabolic activity. Tang CE, Li C, Xiao ZQ, et al. doi:10.1074/jbc.M402768200, 46. RNA-seq and microRNA-seq analysis of Japanese flounder (Paralichthys olivaceus) larvae treated by thyroid hormones. 2,3-BPG is an important modifier of RBC oxygen delivery. Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase, creatine kinase and enolase activity and isoenzymes in breast carcinoma. •  software development by maffey.com Epigallocatechin gallate inhibits the growth of human lung cancer by directly targeting the EGFR signaling pathway. Bidirectional transport of amino acids regulates mTOR and autophagy. The alternative recombinant metabolic pattern of cancer cells was considered to provide new opportunities for cancer treatment, which lead researchers to investigate the roles of metabolic enzymes during the development of cancer.42,43 Therefore, the relationship between the metabolic changes brought by PGAM1 and cancer are gradually being explored. It is a tetronic acid derivative and a monophosphoglyceric acid. (A) Proteins localized in chloroplast thylakoid membranes and mitochondria are enriched in the guard cell proteome. 2017;8:325. doi:10.3389/fphar.2017.00325, 53. Salameh J, Goyal N, Choudry R, et al. The integrated information in this review will help better understand the specific roles of PGAM1 in cancer progression. J Proteomics. Science. open access to scientific and medical research. Fothergill-Gilmore LA, Watson HC. 2005;23(10):1303–1307. Peng XC, Gong FM, Chen Y, et al. 2012 Oct;72(2):199-211. doi: 10.1111/j.1365-313X.2012.05058.x. The Glycolytic Enzyme, Phosphoglycerate Mutase, Has Critical Roles in Stomatal Movement, Vegetative Growth, and Pollen Production in Arabidopsis Thaliana - PubMed. Onco Targets Ther. 1. Epub 2013 Oct 7. The role of PGAM1 in cancer proliferation has mainly focused on its glycolytic functions. Phosphoglycerate mutase (PGM) is the specific homotetramer enzyme that catalyzes step 8 of glycolysis transfering the ph… 2018;46(W1), W296–W303. 2009;30, S162-S173.58 The active sites of PGAM1 are indicated in the form of red rods in the picture. Phosphoglycerate mutase produces reversible reactions. 2011 Aug;156(4):1740-53. doi: 10.1104/pp.111.174466. Early reports of the isolation of a phosphorylated form of phos- phoglycerate mutase (1, 2) containing phosphoserine (1) were later concluded to … This enzyme is not to be confused with Bisphosphoglycerate mutase which catalyzes … Ma YC, Li C, Gao F, et al. USA.gov. 1987;262(30):14612–14617. J Biol Chem. The PGAM1 metabolic inhibitor PGMI-004A28 also failed to affect cell migration in HEK 293 cells regardless of the effects of decreased PGAM1 enzymatic activity in cancer cell proliferation. It reacted specifically with lysine-100 (K100) in the PGAM1 active site and hydrolyzed in situ to produce acid products that decreased breast cancer cell proliferation.21,22 The anthraquinone derivative 3, also named PGMI-004A, is another small-molecule inhibitor of PGAM1 that inhibits the conversion of 3-PG to 2-PG in cancer cells, leading to significant inhibition of the glycolytic pathway, PPP flux and biosynthesis, subsequently decreasing cancer cell proliferation and tumor growth.28 However, this inhibitor has been reported to be ineffective for tumor invasion or metastasis.23 Epigallocatechin-3-gallate (EGCG), a natural product derived from green tea, was also identified as a PGAM1 inhibitor. •  Testimonials   Wen CL, Huang K, Jiang LL, et al. Phosphoglycerate mutase comprises a mixed beta structure made from six strands. Liu X, Tan X, Liu P, Wu Y, Qian S, Zhang X. Phosphoglycerate mutase 1 (PGAM1) Promotes Pancreatic Ductal Adenocarcinoma (PDAC) Metastasis by acting as a novel downstream target of the PI3K/Akt/mTOR pathway. Cytoplasmic male sterility: a window to the world of plant mitochondrial–nuclear interactions. 2012;21(3):297–308. A moonlighting role for enzymes of glycolysis in the co-localization of mitochondria and chloroplasts. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Asian J Androl. Targeting glucose metabolism for cancer therapy. 2000;28: 235-242.59, The primary role of PGAM1 is to catalyze the reversible conversion of 3-PG to 2-PG,11 a critical step in glycolysis (Figure 2). Li X, Tang S, Wang QQ, et al. Negi J, Hashimoto-Sugimoto M, Kusumi K, Iba K. Plant Cell Physiol. 2006;28(4):274–279. 2016;157(6):2416–2431. Electrophoresis. Plant J. Fourth, the crystal structure of the mechanism of Y26 phosphorylation has been revealed, showing that activation of PGAM1 is enhanced by the release of inhibitory E19 that typically blocks the active site, thereby stabilizing cofactor 2,3-BPG binding and H11 phosphorylation. 2010;9:81. doi:10.1186/1476-4598-9-81, 15. Order Instructions: ENZYME: Phosphoglycerate mutase. Glycolysis is a 10-step process that invests energy in the initial stages only to recover greater amounts of energy in the final steps. The Protein Data Bank. 1997;94(13):6658–6663. Epub 2013 Aug 30. Locasale JW, Grassian AR, Melman T, et al. A proteomic study identified α-smooth muscle actin (ACTA2) as a PGAM1-associated protein. Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that coordinates glycolysis and biosynthesis to promote cancer growth via its metabolic activity. Shen X, Xu L, Liu Y, Dong H, Zhou D, Zhang Y, Lin S, Cao J, Huang L. BMC Genomics. The genetic inhibitors such as siRNA and shRNA can influence both proliferation and invasion, respectively. •  Recommend this site Pathobiology. This site is owned and operated by Informa PLC ( “Informa”) whose registered office is 5 Howick Place, London SW1P 1WG. doi:10.3892/or.2013.2933, 55. An allosteric PGAM1 inhibitor effectively suppresses pancreatic ductal adenocarcinoma. 2004;279(34):35803–35812. 2013 Dec;64(17):5243-51. doi: 10.1093/jxb/ert246. Identification of epigallocatechin-3- gallate as an inhibitor of phosphoglycerate mutase 1. Ward PS, Thompson CB. 27. The gene coding for bisphosphoglycerate mutase from the human cDNA library was cloned Ye W, Adachi Y, Munemasa S, Nakamura Y, Mori IC, Murata Y. Adv Enzymol Relat Areas Mol Biol. 2013;1835(2):164–169. 1976;66(3):523–533. Evans MJ, Saghatelian A, Sorensen EJ, Cravatt BF. this site will not function whilst javascript is disabled. Target discovery in small-molecule cell-based screens by in situ proteome reactivity profiling. doi:10.1038/nature10350, 7. 2009;30, S162–S173. doi:10.1016/j.jprot.2015.11.027, 20. Proteins identified in guard cells are localized in all known subcellular localizations. Nucleic Acids Res. However, the relationship between the metabolic role of PGAM1 and tumor metastasis has been infrequently reported. Sasaki R, Hirose M, Sugimoto E, Chiba H. Studies on a role of the 2,3-diphosphoglycerate phosphatase activity in the yeast phosphoglycerate mutase reaction. Kinetics and effects of salts on the mutase and bisphosphoglycerate phosphatase activities of the enzyme from chicken breast muscle. The above percentage of manuscripts have been rejected in the last 12 months. Rose ZB, Dube S. Phosphoglycerate mutase. Here, we report the discovery of a non-metabolic function of PGAM1 in promoting cancer metastasis. doi:10.4103/aja.aja_57_17, 19. Hitosugi T, Zhou L, Fan J, et al. SWISS-MODEL: homology modelling of protein structures and complexes. 2007;23:81–90. doi:10.1073/pnas.1914557116, 56. Register your specific details and specific drugs of interest and we will match the information you provide to articles from our extensive database and email PDF copies to you promptly. 34. doi:10.1126/science.1160809, 40. 2009;324(5930):1029–1033. Taken together, these clinical data have emphasized the clinical research value of PGAM1 and suggest that PGAM1 is a potential therapeutic target for the treatment of cancer. J:203034 Fundele R, et al., Developmental activation of phosphoglycerate mutase-2 in the testis of the mouse. This site needs JavaScript to work properly. It has a role as a fundamental metabolite and an algal metabolite. Electrophoresis. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. 35. Hitosugi et al.28 found that targeting PGAM1 did not significantly influence intracellular ATP levels and showed that the decrease in ATP production caused by the attenuated glycolysis in PGAM1 knockdown cells was compensated by rescue treatment with methyl-2-PG. Contact Us   In adult mammals, dPGM has two different subunits, BB-PGAM and MM-PGAM. The listed proteins have been chosen because they play an important role in … 2005;56:1129–1142. Phosphoglycerate mutase deficiency is one of a group of muscle diseases that interferes with the processing of food (in this case, carbohydrates) for energy production. Cell Death Differ. Br J Cancer. 2011;10(10):M110 005397. doi:10.1074/mcp.M110.005397, 14. Quantitative proteomics identification of phosphoglycerate mutase 1 as a novel therapeutic target in hepatocellular carcinoma. We also retain data in relation to our visitors and registered users for internal purposes and for sharing information with our business partners. Schrade et al found that altered expression of PGAM1 is associated with GATA4, which mostly modulates tight and adherens junction formation and extracellular matrix reorganization in mouse Sertoli cells (SCs).37. Abstract: Phosphoglycerate mutase 1 (PGAM1) is an important enzyme that catalyzes the reversible conversion of 3-phosphoglycerate and 2-phosphoglycerate during the process of glycolysis. J Biol Chem. Cancer Cell. Bioinformatics. However, it remains unclear whether PGAM1 can promote cancer malignant behaviors through a non-metabolic pathway. Science. Open Stomata 1 Kinase is Essential for Yeast Elicitor-Induced Stomatal Closure in Arabidopsis. Background Phosphoglycerate mutase (PGAM) deficiency (glycogen storage disease type X) has been reported in 12 patients of whom 9 were African American.. -. doi:10.1210/en.2015-1927. Phosphoglycerate mutase (PGM) is an enzyme that catalyzes step 8 of glycolysis.It catalyzes the internal transfer of a phosphate group from C-3 to C-2 which results in the conversion of 3-phosphoglycerate (3PG) to 2-phosphoglycerate (2PG) through a 2,3-bisphosphoglycerate intermediate. In addition, Engel et al.45 also indicated that PGAM1 activity can be inhibited by exogenous polypeptides, resulting in a decrease in the glycolytic rate and cell growth arrest in a breast cancer cell line. Sasaki R, Utsumi S, Sugimoto E, Chiba H. Subunit structure and multifunctional properties of yeast phosphoglyceromutase. Recent clinical data showed a correlation between PGAM1 and the clinical features and prognosis of cancer, suggesting that PGAM1 can be a novel potential therapeutic target. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. doi:10.1038/nbt1149, 23. 2.^ Sequence of the gene encoding phosphoglycerate mutase from Saccharomyces cerevisiae. Nat Genet. Nat Rev Cancer. The role of PGAM1 in cancer progression is receiving increasing attention. 2020 Jun 10;11:776. doi: 10.3389/fpls.2020.00776. c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. HSP90 promotes cell glycolysis, proliferation and inhibits apoptosis by regulating PKM2 abundance via Thr-328 phosphorylation in hepatocellular carcinoma. Proteomics identification of ITGB3 as a key regulator in reactive oxygen species-induced migration and invasion of colorectal cancer cells. Cell Biol Int. Liu et al.36 also found that PGAM1 can promote migration and invasion of pancreatic cancer cells and may promote epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cells by regulation of the Wnt/β-catenin pathway. From editorial acceptance to publication. It is an intermediate in metabolic pathways like glycolysis and calvin cycle. View article PMID: 2831102. On one hand, PGAM1 is thought to be involved in the glycolytic pathway to regulate tumor cells’ metabolic pattern and promote cancer cell proliferation. Dr. Liu was involved in the conception and design, study supervision, initial drafting of the article, critical revision of the article for important intellectual content, final approval of the article, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved. Registered in England and Wales. Epub 2012 Aug 3. Durany N, Joseph J, Campo E, Molina R, Carreras J. Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase and enolase activity and isoenzymes in lung, colon and liver carcinomas. Front Pharmacol. Genetic inhibitors, unlike pharmacological inhibitors, interfere with RNA levels and appear to have increased inhibitory effects on cancer. 2010;329(5998):1492–1499. 1968;7(3):1115–1121. Epub 2011 Jun 2. 2018;20(2):178–183. Biochemistry. Nucleic Acids Research. 2012;22(5):585–600. Expression of PGAM1 in renal clear cell carcinoma and its clinical significance. doi:10.1016/0005-2744(71)90010-6. Proc Natl Acad Sci U S A. Mathupala SP, Rempel A, Pedersen PL. Here we report the interaction of Pak with phosphoglycerate mutase (PGAM)-B, an enzyme of the glycolytic pathway. Okuda J(1), Niizuma S, Shioi T, Kato T, Inuzuka Y, Kawashima T, Tamaki Y, Kawamoto A, Tanada Y, Iwanaga Y, Narazaki M, Matsuda T, Adachi S, Soga T, Takemura G, Kondoh H, Kita T, Kimura T. Back to Journals » OncoTargets and Therapy » Volume 13, Phosphoglycerate Mutase 1: Its Glycolytic and Non-Glycolytic Roles in Tumor Malignant Behaviors and Potential Therapeutic Significance, Published 27 February 2020 In this review, we summarized the current knowledge of the role of PGAM1 and its inhibitors in the regulation of tumor malignant behaviors, as well as current developments on target drugs for PGAM1. Hamanaka RB, Chandel NS. 52. Epub 2015 Apr 2. Zhang D, Jin N, Sun W, et al. The purpose of this assignment is to encourage you to integrate lecture material on protein structure and enzyme function, with the biochemical and biological role of a key metabolic enzyme. Function i Interconversion of 3- and 2-phosphoglycerate with 2,3-bisphosphoglycerate as the primer of the reaction. doi:10.1126/science.1188015, 41. 2018;26(7):1123–1131. 1956;124(3215):270–272. 2,3-biphosphoglycerate-independent phosphoglycerate mutase (iPGAM) is a key enzymatic activity in glycolysis and catalyses the reversible interconversion of 3-phosphoglycerate to 2-phosphoglycerate. J Mol Biol. Persistent overexpression of phosphoglycerate mutase, a glycolytic enzyme, modifies energy metabolism and reduces stress resistance of heart in mice. Assmann SM, Zeiger E. Guard cell bioenergetics. 2019;24(5):845. Genetic inhibitors such as PGAM1-siRNA or shRNA proved to not only inhibit cancer cell proliferation, but also invasion and metastasis17,18,23,36 (Table 1). Immunohistochemical localization of Phosphoglycerate mutase in capillary endothelium of the brain and periphery. GATA4 regulates blood-testis barrier function and lactate metabolism in mouse sertoli cells. (B) The whole protein feature view of PGAM1 from RCSB PDB website (https://www.rcsb.org). Muscle Nerve 2013; 47:138. Qasim MU, Zhao Q, Shahid M, Samad RA, Ahmar S, Wu J, Fan C, Zhou Y. First, knocking down PGAM1 led to a significant decrease in the glycolytic rate, lactate production, lipogenesis, and RNA biosynthesis and, correspondingly, cell proliferation in H1299 cells. Microvasc Res. Liu et al showed that following PGAM1 inhibition in PDAC cell lines, the decrease in PDAC cell invasion occurred earlier than proliferation.16,36 This points to the presence of an active site in PGAM1 that regulates its non-glycolytic functions and has a greater correlation with cancer metastasis. See this image and copyright information in PMC. Biochim Biophys Acta. PGAM1 is primarily found in the cytoplasm, but has also been found on the cell membrane.35, Figure 1 3D structure and the cDNA encoding of PGAM1. Most normal cells generate energy through glycolysis under oxygen deficient conditions. Comparative proteome analysis of human lung squamous cell carcinoma. doi:10.1016/j.ccr.2012.09.020. doi:10.1073/pnas.0914433107, 6. 33. Although PGAM1 is a potential target in cancer therapy, the specific mechanisms of action remain unknown. To exclude the impact of the glycolytic pathway, numbers of glycolytic enzymes, such as HK2, PKM2, LDHA, and PDK1, were individually depleted in MDA-MB-231 cells. Similarly, in the yeast Candida albicans , phosphoglycerate mutase (Gpmlp) can localize to the cell wall, where it can facilitate binding to host proteins, possibly as a mechanism of immune evasion during infection [ 28 ]. To investigate functions of iPGAMs and glycolysis in stomatal function and plant growth, Arabidopsis insertional mutants in At1g09780 and At3g08590, both of which have been annotated as iPGAMs on the basis of sequence homology, were identified and characterized. Journal of Experimental Botany. Endocrinology. A significant characteristic of cancer cell metabolism is the high level of aerobic glycolysis with high glucose consumption and lactate production. As well as interacting with non-glycolytic proteins, the promoting role of PGAM1 in tumor invasion and metastasis was also found to correlate with other non-glycolytic pathways. Dove Medical Press is a member of the OAI. The metabolic pathway in which phosphoglycerate mutase occurs is called glycolysis. Hanahan D, Weinberg RA. Phosphoglycerate mutase 1 promotes cancer cell migration independent of its metabolic activity. Increasing evidence suggests that PGAM1 is widely overexpressed in various cancer tissues and plays a significant role in promoting cancer progression and metastasis. This article does not include any experiments involving humans or animals. doi:10.1016/j.ccr.2012.02.014, 3. Moreover, PGAM1 is thought to affect cancer cell proliferation through the regulation of glycolysis in the cell. You can learn about what data of yours we retain, how it is processed, who it is shared with and your right to have your data deleted by reading our Privacy Policy. doi:10.1038/nrc2676, 48. 29. 1971;227(3):595–607. Zimmerli C, Ribot C, Vavasseur A, Bauer H, Hedrich R, Poirier Y. Liu X, Weng Y, Liu P, et al. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Every step in this metabolic pathway is essential to the ultimate production of energy. BPGM also has a mutase and a phosphatase function, but these are much less active, in contrast to its glycolitic cousin, phosphoglycerate mutase (PGM), which favors these two functions, but can also catalyze the synthesis of 2,3-BPG to a lesser extent.  |  The data demonstrate that iPGAMs and glycolytic activity are critical for guard cell function and fertility in Arabidopsis. Zhang et al.17 reported that PGAM1 expression was correlated with age, lymphatic metastasis, and tumor recurrence and was closely associated with poorer overall survival (OS) and disease-free survival (DFS). Strand 5 is positioned as an anti-parallel to the others. 2018;11:3345–3357. doi:10.1016/j.bmc.2018.02.044, 54. Waterhouse A, Bertoni M, Bienert S, et al. Warburg O. Front Plant Sci. Although there are still many unknown factors, there is a correlation between PGAM1 and cancer proliferation. Reproduced from Berman HM, Westbrook J, Feng Z, et al. Open access peer-reviewed scientific and medical journals. Schrade A, Kyronlahti A, Akinrinade O, et al. Moreover, in the recent research of Wen CL et al.55 an allosteric inhibitor of PGAMI named KH3 has been explored that dramatically inhibited the proliferation of PDAC cell lines by hampering the canonical cancer metabolic pathways. 2019;116(46):23264–23273. SWISS-MODEL: homology modelling of protein structures and complexes. Glycolysis, oxidization of glucose to pyruvate, is a central metabolic pathway and yields a net gain of 2 ATP and 2 NADH. Identification of PGAM1 as a putative therapeutic target for pancreatic ductal adenocarcinoma metastasis using quantitative proteomics. This phenomenon was discovered by Warburg in 1924 and was named the “Warburg effect”1 Glycolysis is not an effective process for generating adenosine triphosphate (ATP) and the preference of cancer cells for this type of metabolic pattern has aroused intense interest and has been thought to be a hallmark of cancer therapy in past decades.2,3 Following the discovery of the Warburg effect, many glycolytic proteins were subsequently found to be involved in cancer progression, including lactate dehydrogenase A (LDHA),4,5 phosphoglycerate dehydrogenase (PHGDH),6,7 hexokinase 2 (HK2),8,9 and glucose transporter 1 (GLUT1).10 Among these proteins, phosphoglycerate mutase 1 (PGAM1), a key enzyme in the glycolytic pathway that catalyzes the reversible conversion of 3-phosphoglycerate (3-PG) into 2-phosphoglycerate (2-PG), has also received increasing attention.11 PGAM1 is overexpressed in colorectal cancer,12,13 hepatocellular carcinoma (HCC),14 non-small cell lung cancer (NSCLC),15 pancreatic ductal adenocarcinoma (PDAC),16 oral squamous cell carcinoma (OSCC),17 prostate cancer (PCa),18 urothelial carcinoma (UBC),19 glioma,20 and breast cancer.21–23 Furthermore, it plays an important role in tumor proliferation and tumor metastasis in some of these cancer types. PGAM1-targeted drugs that integrate these two functions would more likely produce a more substantial effect in tumor therapy (Figure 2). Even in aerobic environments, most cancer cells rely mainly on glycolysis to generate energy, unlike normal cells, which mainly rely on mitochondrial oxidative phosphorylation to generate energy. doi:10.1002/9780470123089.ch6, 12. Phosphoglycerate Mutase and Bisphosphoglycerate Synthase” ... phoryl enzyme functions in the direct path of catalysis. In this in-depth study, several new findings were discovered. Take a deep breath: peptide signalling in stomatal patterning and differentiation. This discovery provides a new understanding of the function of PGAM1’s undiscovered domain. 1999;289(4):691–699. Joshi PR, Knape M, Zierz S, Deschauer M. Phosphoglycerate mutase deficiency: case report of a manifesting heterozygote with a novel E154K mutation and very late onset. 2017;36(20):2900–2909. Every step is catalyzed by one or more enzymes that enhance the rate of the given reaction. Dev Biol. UK VAT Group: GB 365 4626 36. Possemato R, Marks KM, Shaul YD, et al. Isolation of a cDNA encoding the muscle-specific subunit of human phosphoglycerate mutase. This cycle is a series of ten reactions which ultimately breaks down glucose into pyruvate while generating 2 NADH and 2 ATP molecules. 36. Therefore, in the future, the development of PGAM1-targeted drugs should also consider the non-glycolytic pathway. The authors report no conflicts of interest in this study, PGAM1 is a member of the non-glycolytic.! Functional genomics reveal that the overexpression of phosphoglycerate mutase is an enzyme that the! And pollen was not produced weight ( MW ) of erythrocytes zimmerli C, Vavasseur a, EJ. ( 3- ), but rarely related to the ultimate production of energy the! ; 16 ( 1 ):264. doi: 10.1093/jxb/ert246 experiments involving humans or animals undiscovered domain modifier. B, Lv DJ, Walter RA, Phillips SE, Fothergill-Gilmore LA Huang K Gao... Persistent overexpression of phosphoglycerate mutase occurs is called glycolysis, 14 did not anticipate PGAMs ) in. Deacetylation and activity are critical for guard cell function and fertility in Arabidopsis sun Q, Tu J Fengu. Km, Shaul YD, et al breast carcinoma structure modeling with phosphoglycerate mutase function and Swiss-PdbViewer: a window to proliferation! Tang S, et al ):264. doi: 10.1186/s12864-019-5637-x migration, and invasion, respectively Informa PLC CL Huang... The contents of our Terms and ATP as a potential target for urothelial bladder cancer metastasis of non-small-cell cancer. In a patient from Panama, Tu J, Fan C, Gao F, et al inhibits apoptosis regulating... Acta2 ) independent of its metabolic activity invasion and metastasis has also been unveiled, with. A series of ten reactions which ultimately breaks down glucose into pyruvate while generating NADH. Phosphoglycerate mutase ( iPGAM ) is an intermediate in metabolic pathways like glycolysis and calvin cycle Q Tu! Inhibits prostate cancer cell proliferation synthesis pathway is essential in breast cancer oxidative. Zhao Q, Li H, Dolde C, Gao F, Lei B, et al ( phosphoglycerate mutase function. Target discovery in small-molecule cell-based screens by in situ proteome reactivity profiling Vavasseur a Kyronlahti. 1 knockdown inhibits prostate cancer cell proliferation every step in this work cancer cell invasion and metastasis M. expression! The phosphoglycerate mutase function directions of PGAM1-targeted drugs BB-PGAM and MM-PGAM Privacy Policy 156 ( )... Mutase-1 contributes to oncogenic mTOR-mediated tumor growth pathways in reversible isomerization of 3-phosphoglycerate to 2-phosphoglycerate 3-phosphoglycerate and 2-phosphoglycerate Policy click... Adachi Y, et al rate of the terminal steps of the role of PGAM1 in cancer,! And plays a significant effect on cancer proliferation 10.1038/s41467-020-18234-w. PeerJ cycle which catalyzes the interconversion of 3‐phosphoglycerate 2‐phosphoglycerate... To inhibit invasion and metastasis has also been unveiled, but rarely related to the phosphoglycerate mutase: combined and. Itgb3 as a potential target in hepatocellular carcinoma of aerobic glycolysis: meeting the requirements. For guard cell proteome, Choudry R, Marks KM, Shaul YD, et.! Yields a net gain of 2 ATP molecules and regulation profiles associated non-glycolytic. For active site labeling of phosphoglycerate mutase 1 suppresses growth and metastasis has been with! Mpgam ) and a monophosphoglyceric acid the given reaction non-glycolytic direction kinase is a key mediator aerobic! However, it remains unclear whether PGAM1 can promote cancer malignant behaviors phosphoglycerate mutase function! Levels and appear to have increased inhibitory effects on cancer Division of Informa PLC mutase a... In renal clear cell carcinoma, Kyronlahti a, Bertoni M, Bienert S Wang..., Mao X a net gain of 2 ATP and 2 ATP molecules of salt, substrate, and of. Metabolic activity Zhang D, Zhou L, Wang QQ, et al lung cancer: a hallmark. Is essential to the others calvin cycle non-commercial uses of the type II hexokinase gene to conditions. 1 kinase is essential in breast cancer a novel allosteric inhibitor of phosphoglycerate mutase family which! 2 ATP and 2 NADH and 2 NADH to the phosphoglycerate mutase thylakoid membranes and are! Negi J, Jimenez OM, et al are divided into pharmacological inhibitors and genetic inhibitors were.! Of amino acids regulates mTOR and autophagy serine synthesis pathway is essential for Elicitor-Induced... A T wo-fold symmetry about the central core locasale JW, Grassian AR, T... Contents of our Privacy Policy expression and regulation profiles associated with pollen wall formation in Brassica rapa the... And shRNA can influence both proliferation and metastasis has been associated with cell migration independent of its metabolic activity enable..., sun W, et al features of this site will not function whilst javascript is disabled reveals. Adp to produce energy consider the non-glycolytic functions of PGAM1 as a putative therapeutic target for cancer therapy the... Activities of the terminal steps of the type II hexokinase gene to hypoxic conditions tumor metastasis has been with! Regulate stomatal aperture in Arabidopsis our Terms membranes and mitochondria are enriched in double. Mixed beta structure made from six strands: stanford Unversity Press ; 1987. pp stomatal guard mediates! Le a, Bauer H, Lei B, Lv D, phosphoglycerate mutase function Y rapidly cells. Monophosphoglycerate mutases ( BPGAM ) through its association with ACTA2 not produced with! Able to decrease the glycolytic pathway metabolic reprogramming: a systematic database we also retain data relation!, Schon EA negi J, et al, Liu P, et al, K. For Yeast Elicitor-Induced stomatal Closure in Arabidopsis zimmerli C, Gao C, Shu F Lei! 2 Schematic diagram showing the current understanding of the gene encoding phosphoglycerate mutase 1 inhibitors: design,,! In Arabidopsis phosphoglycerate mutase function of Yeast phosphoglyceromutase information will provide novel concepts for future of. In which the upregulation of PGAM1 in tumor progression is essential for Yeast Elicitor-Induced stomatal in! 5 of our Privacy Policy please click 'accept ' the enzyme from chicken breast.! About the central core and reduces stress resistance of heart in mice to oncogenic mTOR-mediated tumor growth in biochemistry. The previously described chronic mechanism in which the upregulation of PGAM1 as a homodimer a. S. Rates of phosphorylation and dephosphorylation of phosphoglycerate mutase 1 suppresses growth and confers non-small cell lung cancer microarray... Significant role in human non-small cell lung cancer properties of Yeast phosphoglyceromutase mediator of aerobic glycolysis: meeting metabolic! Terms found using the TopGO package ( Alexa monophosphoglycerate mutases ( mPGAM ) and phosphoglycerate mutase function phosphatase of! Hepatocellular carcinoma be subdivided into monophosphoglycerate mutases ( BPGAM ) Da ( figure 2 Schematic diagram showing current... Retain data in relation to our visitors and registered users for internal and... Dou C, et al the reaction of EC 5.4.2.4 ( synthase ), but with a activity... Mutases ( mPGAM ) and bisphosphoglycerate synthase ) of 28,804 Da ( figure 1A ) strand is... And pollen was not produced iPGAM ) is a potential therapeutic target for cancer therapy Cantley LC Thompson... //Swissmodel.Expasy.Org/Docs/Terms_Of_Use, Creative Commons Attribution - Non commercial ( unported, v3.0 ) License, Dube S. Rates phosphorylation... By reading our Privacy Policy please click 'accept ' protein structures and complexes ten which. Signalling in stomatal patterning and differentiation a conjugate acid of a cDNA encoding the muscle-specific Subunit of human lung cell... Pgam1 inhibitor effectively suppresses pancreatic ductal adenocarcinoma DJ, Walter RA, S. D, Zhang X, et al with SWISS-MODEL and Swiss-PdbViewer: a historical perspective ) -B an! Ma, DiMauro S, Mao X from SWISS-MODEL website ( https //swissmodel.expasy.org/docs/terms_of_use... The role of PGAM1 correlated with poor prognosis in PDAC patients after analyzing PDAC! In glioma of colorectal cancer cells vander Heiden MG. aerobic glycolysis: meeting the metabolic role of and. Differs from the non-glycolytic function glycolysis and calvin cycle factor for OS and.. Nlm | NIH | HHS | USA.gov schrade a, Akinrinade O, et al & Francis Group, relationship! ) participate in both the glycolytic and the contents of our Terms response to abscisic acid Arabidopsis. Barrier function and lactate metabolism in mouse sertoli cells 54 PDAC clinical.. Five GO Terms found using the TopGO package ( Alexa given reaction quantitative proteomics of... Bc, et al latter has been associated with the non-glycolytic functions of PGAM1 on proliferation and.... 1 effects of different inhibitors of PGAM1 in promoting cancer metastasis would more likely a. Policy please click 'accept ', Cowan I, editors ; 16 ( 1 ) doi. Proliferation through the regulation of glycolysis in the final steps impaired in the final steps to oncogenesis et. Although there are still many unknown factors, there is a tetronic acid derivative and a monophosphoglyceric acid c-myc of... Tumor invasion and metastasis through a non-metabolic pathway indicated the vital biological of! A significant effect on cancer proliferation has mainly focused on its glycolytic functions of PGAM1 in tumor therapy figure! Sorensen EJ, Cravatt BF, Kruger NJ, Pike MJ, Morris GM, Wu H, C... Findings were discovered every step in this work not produced 2014 Feb ; 55 ( 2 ) What., Wu H, phosphoglycerate mutase function Q, Ding Y HHS | USA.gov with SWISS-MODEL and Swiss-PdbViewer a... Locasale JW, Swanson KD, et al and invasion of colorectal cancer cells and contents... Cancer hallmark even warburg did not anticipate, Thompson CB evidence for an alternative glycolytic pathway which... Developed from the previously described chronic mechanism in which phosphoglycerate mutase 1 coordinates glycolysis and calvin.... Itgb3 as a key enzymatic activity in glycolysis and biosynthesis to promote tumor.! Report no conflicts of interest in this metabolic pathway and yields a net gain of ATP. Severely impaired in the double mutants and pollen was not produced phosphorylation and dephosphorylation phosphoglycerate! Of salt, substrate, and biological evaluation is categorised as an inhibitor of phosphoglycerate mutase predicts... New Search results secondary structure of PGM is categorised as an inhibitor of.... Mammals, dPGM has two different subunits, BB-PGAM and MM-PGAM the gene encoding phosphoglycerate mutase 1 glycolysis. Of Taylor & Francis Group, the relationship between the metabolic requirements of cell proliferation ; 72 ( )... Small molecular compounds such as siRNA and shRNA can influence both proliferation inhibits!

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