In this study, PGAM1 was found to directly interact with α-smooth muscle actin 2 (ACTA2) independent of its metabolic activity. -. Phosphoglycerate mutase (PGAM) catalyzes one of the terminal steps of the glycolytic pathway, the interconversion of 2-phosphoglycerate and 3-phosphoglycerate. Plant Cell Physiol. Trends in Genetics. 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. All dPGMs, whether monomeric, dimeric, or tetrameric, have the same essential activity; however, they differ in their quaternary assemblies (2). 2017;8:325. doi:10.3389/fphar.2017.00325, 53. Peng XC, Gong FM, Chen Y, et al. Huang K, Jiang L, Li H, Ye D, Zhou L. Development of anthraquinone analogues as phosphoglycerate mutase 1 inhibitors. Schrade A, Kyronlahti A, Akinrinade O, et al. 2011;208(2):313–326. doi:10.1210/en.2015-1927. 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. Stomatal function. Lei Y, Huang K, Gao C, et al. doi:10.1039/b705113a, 22. 32. J Biol Chem. Most small molecular compounds such as PGMI-004A usually have a significant effect on cancer proliferation. doi:10.1038/s41418-017-0034-y, 16. Hitosugi T, Zhou L, Fan J, et al. Bisphosphoglycerate mutase is a trifunctional enzyme of which the main function is to synthesize 2,3-bisphosphoglycerate, the allosteric effector of hemoglobin. Stomatal movements require massive changes in guard cell osmotic content, and both stomatal opening and stomatal closure have been shown to be energy-requiring processes., Creative Commons Attribution - Non Commercial (unported, v3.0) License. 58. In this in-depth study, several new findings were discovered. Bisphosphoglycerate mutase (BPGM) is an enzyme unique to erythrocytes and placental cells. doi:10.1006/jmbi.1999.2848. 2010;329(5998):1492–1499. 59. Phosphoglycerate mutase 1 knockdown inhibits prostate cancer cell growth, migration, and invasion. 2020 Jun 10;11:776. doi: 10.3389/fpls.2020.00776. (A) Proteins localized in chloroplast thylakoid membranes and mitochondria are enriched in the guard cell proteome. Proteins identified in guard cells are localized in all known subcellular localizations. An allosteric PGAM1 inhibitor effectively suppresses pancreatic ductal adenocarcinoma. 2015 Jun;56(6):1239-48. doi: 10.1093/pcp/pcv051. J Biol Chem. 2012;22(5):585–600. Persistent overexpression of phosphoglycerate mutase, a glycolytic enzyme, modifies energy metabolism and reduces stress resistance of heart in mice. Electrophoresis. Salameh J, Goyal N, Choudry R, et al. Fish Physiol Biochem. Zimmerli C, Ribot C, Vavasseur A, Bauer H, Hedrich R, Poirier Y. Huang K, Liang Q, Zhou Y, et al. In addition to the proliferation of tumor cells, tumor metastasis is also an important factor affecting the prognosis of cancer patients. 2017;36(20):2900–2909. Huang et al.51 revealed that F22, K100, and R116 of PGAM1 residues were critical for the binding of inhibitors and that compound 9i, an anthraquinone inhibitor, significantly decreased lung cancer cell proliferation in different cell lines, which is a promising inhibitor for PGAM1. Reproduced from Waterhouse A, Bertoni M, Bienert S, et al. Hitosugi T, Zhou L, Elf S, et al. 2010;9:81. doi:10.1186/1476-4598-9-81, 15. Ren F, Wu H, Lei Y, et al. doi:10.1038/onc.2016.446, 24. A possible role for glycolysis in contributing to the energetic, reducing requirements, or signalling processes regulating stomatal movements has not been investigated previously. Comparative proteome analysis of human lung squamous cell carcinoma. In summary, inhibitors targeting PGAM1 have been developed rapidly. Jacobowitz DM, Jozwik C, Fukuda T, Pollard HB. Proc Natl Acad Sci U S A. Clipboard, Search History, and several other advanced features are temporarily unavailable. Ma YC, Li C, Gao F, et al. Here, we report the discovery of a non-metabolic function of PGAM1 in promoting cancer metastasis. Berman HM, Westbrook J, Fengu Z, et al. Nicklin P, Bergman P, Zhang B, et al. The above percentage of manuscripts have been rejected in the last 12 months. We offer real benefits to our authors, including fast-track processing of papers. 39. 28. Cell. Phosphoglycerate mutase 2 , Phosphoglycerate mutase 1 , Phosphoglycerate mutase 3 (GPM3) Enolase 2 ( ENO2 ) , Enolase-related protein 2 ( ERR2 ) , Enolase-related protein 1 ( ERR1 ) , Enolase-related protein 3 ( ERR3 ) , Enolase 1 ( ENO1 ) doi:10.7150/jca.19278, 18. doi:10.1038/bjc.1997.168, 25. 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. View article PMID: 2831102. doi:10.1159/000245893. doi:10.1038/nrc2676, 48. SWISS-MODEL: homology modelling of protein structures and complexes. Epub 2012 Aug 3. Electrophoresis. The role of PGAM1 in cancer invasion and metastasis was newly found to be mainly associated with non-glycolytic molecules and pathways. It has a role as a fundamental metabolite and an algal metabolite. Bioinformatics. According to a study by Liu et al,36 PGAM1 is a downstream target of the PI3K/Akt/mTOR/HIF-1α pathway, which regulates cellular metabolism (Figure 2). Zhang D, Jin N, Sun W, et al. 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. However, the relationship between the metabolic role of PGAM1 and tumor metastasis has been infrequently reported. doi:10.1126/science.1160809, 40. Liu L, Wang S, Zhang Q, Ding Y. 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. 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. Assmann SM, Zeiger E. Guard cell bioenergetics. Cofactor-dependent phosphoglycerate mutase exists as a homodimer composed of alpha/beta subunits with a t wo-fold symmetry about the central core. Bidirectional transport of amino acids regulates mTOR and autophagy. 33. doi: 10.7717/peerj.9107. Szablewski L. Expression of glucose transporters in cancers. Future studies should focus on the molecular pathways modulated by PGAM1 to induce cancer cell motility during invasion and metastasis and development of drugs that can target the non-glycolytic functions of PGAM1, as its metabolic changes are mainly associated with cancer cell proliferation. 2015;8(8):9410–9415. doi:10.1126/science.123.3191.309, 2. 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. Phosphoglycerate kinase is the seventh enzyme in the cycle which catalyzes the reaction of 1,3-Biphosphoglycerate and ADP to produce 3-Phosphoglycerate and ATP. Science. Int J Clin Exp Pathol. Sun Q, Li S, Wang Y, et al. 2018;26(7):1123–1131. Acta Neuropathol 2009; 117:723. What are the symptoms of phosphoglycerate mutase deficiency? Phosphoglycerate mutase Enzyme. 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. Polyanionic inhibitors of phosphoglycerate mutase: combined structural and biochemical analysis. Buhrens RI, Amelung JT, Reymond MA, Beshay M. Protein expression in human non-small cell lung cancer: a systematic database. doi:10.1073/pnas.94.13.6658, 5. 2018;46(W1), W296–W303. Chin J Cancer. (A) iPGAM1 and…, NLM Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that coordinates glycolysis and biosynthesis to promote cancer growth via its metabolic activity. What is phosphoglycerate mutase deficiency (glycogenosis type 10)? Javascript is currently disabled in your browser. 1. This discovery provides a new understanding of the function of PGAM1’s undiscovered domain. Previously, metabolites such as adenosine monophosphate (AMP), an allosteric activator for AMP-activated protein kinase which senses intracellular energy levels (ATP/AMP ratio), have been suggested to function as signaling molecules.47 Glutamine, which activates leucine uptake, leads to mTOR activation.48 The non-glycolytic role of PGAM1 has been recently uncovered. 2019 Apr 3;20(1):264. doi: 10.1186/s12864-019-5637-x. 2018;46(W1), W296-W30357 and Guex N, Peitsch MC, Schwede T. Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: A historical perspective. 2020 Jun 29;8:e9107. 2005;23(10):1303–1307. 2010;107(5):2037–2042. 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. Bioorg Med Chem. Asian J Androl. Numbers…, Proteins involved in energy provision are enriched in the identified guard cell proteome.…, Double ipgam1 ipgam2 mutants have no detectable iPGAM enzyme activity. Dec ; 64 ( 17 ):5243-51. doi: 10.1038/s41467-020-18234-w. PeerJ with prognosis. Confirmed that PGAM1 can promote tumor metastasis has been verified through its association with.... One or more enzymes that enhance the rate of the non-glycolytic function and.:264. doi: 10.1093/pcp/pcv051 has mainly focused on its glycolytic functions Genes Sclerotinia. Include any experiments involving humans or animals structural requirements for active site labeling of mutase. Peitsch MC, Schwede T. 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