1976;66(3):523–533. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Identification of PGAM1 as a putative therapeutic target for pancreatic ductal adenocarcinoma metastasis using quantitative proteomics. Clipboard, Search History, and several other advanced features are temporarily unavailable. MJE3 was the first cell-permeable, small-molecule compound inhibitor of PGAM1. Hitosugi T, Zhou L, Elf S, et al. Identification of epigallocatechin-3- gallate as an inhibitor of phosphoglycerate mutase 1. doi:10.1016/j.cellbi.2008.07.004, 13. Phosphoglycerate mutase produces reversible reactions. Every step in this metabolic pathway is essential to the ultimate production of energy. The data demonstrate that iPGAMs and glycolytic activity are critical for guard cell function and fertility in Arabidopsis. 30. Li C, Shu F, Lei B, Lv D, Zhang S, Mao X. Open Stomata 1 Kinase is Essential for Yeast Elicitor-Induced Stomatal Closure in Arabidopsis. Glycolysis, oxidization of glucose to pyruvate, is a central metabolic pathway and yields a net gain of 2 ATP and 2 NADH. Background Phosphoglycerate mutase (PGAM) deficiency (glycogen storage disease type X) has been reported in 12 patients of whom 9 were African American.. It is difficult to confirm whether the mechanisms by which PGAM1 affects tumor metastasis are also achieved through glycolytic regulation. Phophoglycerate mutase 1 (PGAM1) is an enzyme that catalyzes the interconversion of 3‐phosphoglycerate and 2‐phosphoglycerate during glycolysis. • Web Design by Adhesion. PGAM1 was also suggested to be an independent risk factor for OS and DFS. doi:10.1054/bjoc.1999.0871, 26. Microvasc Res. 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/. 1968;7(3):1115–1121. PGAM1 belongs to the phosphoglycerate mutase family, which can be subdivided into monophosphoglycerate mutases (mPGAM) and bisphosphoglycerate mutases (BPGAM). Int J Clin Exp Pathol. doi:10.4103/aja.aja_57_17, 19. 2010;9:81. doi:10.1186/1476-4598-9-81, 15. 1987 Dec;124(2):562-6 Cell. 1997;75(7):969–977. 2011;27:441–464. Nucleic Acids Res. Rose ZB, Dube S. Phosphoglycerate mutase. Phosphoglycerate mutase (PGAM) catalyzes one of the terminal steps of the glycolytic pathway, the interconversion of 2-phosphoglycerate and 3-phosphoglycerate. doi:10.1146/annurev-cellbio-092910-154237, 44. Proteomics identification of PGAM1 as a potential therapeutic target for urothelial bladder cancer. PGAM1 inhibitors are divided into pharmacological inhibitors and genetic inhibitors. 2010;107(5):2037–2042. Immunohistochemical localization of Phosphoglycerate mutase in capillary endothelium of the brain and periphery. Proteomics identification of ITGB3 as a key regulator in reactive oxygen species-induced migration and invasion of colorectal cancer cells. Contact Us   Dove Medical Press is part of Taylor & Francis Group, the Academic Publishing Division of Informa PLC It derives from a glyceric acid. 2012;21(3):297–308. It also correlated with a poor differentiation status and was identified as a potential therapeutic target for urothelial cancer by Peng et al.19 who conducted a two-dimensional electrophoresis proteomic analysis of clinical tissues. doi:10.3892/or.2013.2933, 55. 29. Evidence for an alternative glycolytic pathway in rapidly proliferating cells. 2018;20(2):178–183. 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. Le A, Cooper CR, Gouw AM, et al. 2011;208(2):313–326. Take a deep breath: peptide signalling in stomatal patterning and differentiation. Nucleic Acids Research. 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. 2000;28:235–242. Journal of Experimental Botany. Strand 5 is positioned as an anti-parallel to the others. Hitosugi et al.28,44 found that PGMI-004A, a small molecule inhibitor of PGAM1, was able to decrease the glycolytic function of PGAM1. SWISS-MODEL: homology modelling of protein structures and complexes. Hamanaka RB, Chandel NS. Such information will provide novel concepts for future investigation of PGAM1 as a potential target for cancer therapy. open access to scientific and medical research. Therefore, in the future, the development of PGAM1-targeted drugs should also consider the non-glycolytic pathway. Numbers…, Proteins involved in energy provision are enriched in the identified guard cell proteome.…, Double ipgam1 ipgam2 mutants have no detectable iPGAM enzyme activity. Negi J, Hashimoto-Sugimoto M, Kusumi K, Iba K. Plant Cell Physiol. However, most of the PGAM1 inhibitors were glycolysis-targeted with minimal to no effect on the invasion and metastasis of cancer cells (Table 1). The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Tyr26 phosphorylation of PGAM1 provides a metabolic advantage to tumours by stabilizing the active conformation. Mutase Structure The secondary structure of PGM is categorised as an alpha/beta protein, which has three alpha, beta, alpha layers. Influence of salt, substrate, and cofactor concentrations on the kinetic and mechanistic behavior of phosphoglycerate mutase. In summary, inhibitors targeting PGAM1 have been developed rapidly. The role of PGAM1 in cancer progression is receiving increasing attention. Bioorg Med Chem. •  Top, © Copyright 2021  •  Dove Press Ltd   Phosphoglycerate mutase (PGM) is the specific homotetramer enzyme that catalyzes step 8 of glycolysis transfering the ph… Chin J Cancer. While single mutants were indistinguishable from the wild type in all plant phenotypes assayed, double mutants had no detectable iPGAM activity and showed defects in blue light-, abscisic acid-, and low CO(2)-regulated stomatal movements. 1976;251(16):4817–4822. SWISS-MODEL: homology modelling of protein structures and complexes. Phosphoglycerate mutase is an enzyme that has an very important role in human biochemistry and across many different taxa. Trends in Genetics. 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. Hanahan D, Weinberg RA. Assmann SM, Zeiger E. Guard cell bioenergetics. Nat Commun. Shen X, Xu L, Liu Y, Dong H, Zhou D, Zhang Y, Lin S, Cao J, Huang L. BMC Genomics. 2011;10(10):M110 005397. doi:10.1074/mcp.M110.005397, 14. Phosphoglycerate mutase 1 predicts the poor prognosis of oral squamous cell carcinoma and is associated with cell migration. Table 1 Effects of Different Inhibitors of PGAM1 on Proliferation and Metastasis of Various Cancer. Nat Commun. Bioinformatics. Phosphoglycerate Mutase and Bisphosphoglycerate Synthase” ... phoryl enzyme functions in the direct path of catalysis. Comparative transcriptome analysis and ChIP-sequencing reveals stage-specific gene expression and regulation profiles associated with pollen wall formation in Brassica rapa. 2017;8:325. doi:10.3389/fphar.2017.00325, 53. If you agree to our use of cookies and the contents of our Privacy Policy please click 'accept'. 2012 Oct;72(2):199-211. doi: 10.1111/j.1365-313X.2012.05058.x. 2008;32(10):1215–1222. EGCG was reported to inhibit PGAM1 enzymatic activity by directly impairing glycolysis and PPP flux, regardless of 3-PG competition, and further, it was shown to inhibit cancer cell proliferation by modulating the intracellular level of 2-PG.52 However, because of its multiple targets, its specificity to PGAM1 is poor.28,54 Wang et al.53 used scaffold hopping and a sulfonamide reversal strategy based on the lead compound PGMI-004A to discover a series of xanthone derivatives (12a–12s) as novel PGAM1 inhibitors. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Increasing evidence has indicated the vital biological roles of PGAM1 in tumor progression. 2009;30, S162-S173.58 The active sites of PGAM1 are indicated in the form of red rods in the picture. Cell. Proc Natl Acad Sci U S A. Proc Natl Acad Sci U S A. 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. Phosphoglycerate kinase is a crucial enzyme in the glycolysis cycle. Zhang et al.17 showed that reduced expression of PGAM1 in HN12 and Cal27 cells lead to a significant decrease in cell migration and in the expression levels of corresponding regulatory pathway molecules, such as focal adhesion kinase, the proto-oncogene c-SRC, and paxillin. Epub 2011 Jun 2. J Exp Med. 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