Most normal cells generate energy through glycolysis under oxygen deficient conditions. Sun Q, Li S, Wang Y, et al. this site will not function whilst javascript is disabled. Reproduced from Waterhouse A, Bertoni M, Bienert S, et al. Bidirectional transport of amino acids regulates mTOR and autophagy. However, it remains unclear whether PGAM1 can promote cancer malignant behaviors through a non-metabolic pathway. doi:10.1084/jem.20120162, 43. COVID-19 is an emerging, rapidly evolving situation. 2007;3(7):495–506. J Exp Med. doi:10.1159/000245893. All dPGMs, whether monomeric, dimeric, or tetrameric, have the same essential activity; however, they differ in their quaternary assemblies (2). 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. Phosphoglycerate kinase is a crucial enzyme in the glycolysis cycle. 2018;25(6):1160–1173. 2020 Sep 9;11(1):4509. doi: 10.1038/s41467-020-18234-w. PeerJ. Vander Heiden MG, Cantley LC, Thompson CB. •  Privacy Policy   Plant Physiol. 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. PGAM1 is a homodimer with a molecular weight (MW) of 28,804 Da (Figure 1A). Mechanistic and structural requirements for active site labeling of phosphoglycerate mutase by spiroepoxides. Adv Enzymol Relat Areas Mol Biol. 2010;185:649–662. Phosphoglycerate mutase 1 predicts the poor prognosis of oral squamous cell carcinoma and is associated with cell migration. doi:10.1016/j.bmc.2018.02.044, 54. Kinetics and effects of salts on the mutase and bisphosphoglycerate phosphatase activities of the enzyme from chicken breast muscle. J Biol Chem. doi:10.1016/j.ccr.2012.09.020. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Quantitative proteomics identification of phosphoglycerate mutase 1 as a novel therapeutic target in hepatocellular carcinoma. The promoting role of PGAM1 on tumor metastasis has also been unveiled, but rarely related to the glycolytic functions of PGAM1. Zhang Y, Sampathkumar A, Kerber SM, Swart C, Hille C, Seerangan K, Graf A, Sweetlove L, Fernie AR. c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. The phosphoglycerate mutases. The authors report no conflicts of interest in this work. https://swissmodel.expasy.org/docs/terms_of_use, Creative Commons Attribution - Non Commercial (unported, v3.0) License. 2017;36(20):2900–2909. Dove Medical Press is a member of the OAI. PHO1 expression in guard cells mediates the stomatal response to abscisic acid in Arabidopsis. In order to provide our website visitors and registered users with a service tailored to their individual preferences we use cookies to analyse visitor traffic and personalise content. Wen YA, Zhou BW, Lv DJ, et al. doi:10.1038/nrc2676, 48. A novel allosteric inhibitor of phosphoglycerate mutase 1 suppresses growth and metastasis of non-small-cell lung cancer. An allosteric PGAM1 inhibitor effectively suppresses pancreatic ductal adenocarcinoma. However, the relationship between the metabolic role of PGAM1 and tumor metastasis has been infrequently reported. J Cancer. Phosphoglycerate mutase 1 promotes cancer cell migration independent of its metabolic activity. UK VAT Group: GB 365 4626 36. Ma YC, Li C, Gao F, et al. Phosphoglycerate Mutase In this essay assignment, I have researched the enzyme that is known as phosphoglycerate mutase. Liu L, Wang S, Zhang Q, Ding Y. PGAM1 deacetylation and activity are directly controlled by Sirt1. Stomatal function. Increasing evidence suggests that PGAM1 is widely overexpressed in various cancer tissues and plays a significant role in promoting cancer progression and metastasis. Phosphoglycerate mutase isozyme marker for tissue differentiation in man. Glycolysis, oxidization of glucose to pyruvate, is a central metabolic pathway and yields a net gain of 2 ATP and 2 NADH. Comparative transcriptome analysis and ChIP-sequencing reveals stage-specific gene expression and regulation profiles associated with pollen wall formation in Brassica rapa. 2009;9(8):563–575. 1987 Dec;124(2):562-6 Dev Biol. 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. BPG-independent phosphoglycerate mutase, domain B superfamily 79 311 1.7E-83 TIGRFAM TIGR01307 pgm_bpd_ind: phosphoglycerate mutase (2,3-diphosphoglycerate-independent) IPR005995: Phosphoglycerate mutase, 2,3-bisphosphoglycerate-independent 6 512 0.0 Gene3D The pharmacological inhibitors are small molecular compounds, with six types of small molecules reported to inhibit PGAM1, and which are mainly associated with metabolism and cancer cell proliferation. Phosphoglycerate mutase (PGAM) catalyzes one of the terminal steps of the glycolytic pathway, the interconversion of 2-phosphoglycerate and 3-phosphoglycerate. doi:10.1038/s41418-017-0034-y, 16. In adult mammals, dPGM has two different subunits, BB-PGAM and MM-PGAM. Fothergill-Gilmore LA, Watson HC. Proteomics identification of PGAM1 as a potential therapeutic target for urothelial bladder cancer. 2010;107(5):2037–2042. 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. 1971;227(3):595–607. Cell Metab. It has a role as a fundamental metabolite and an algal metabolite. (A) iPGAM1 and…, NLM doi:10.1126/science.123.3191.309, 2. During glycolysis, the simple sugar glucose is broken down to produce energy. Such information will provide novel concepts for future investigation of PGAM1 as a potential target for cancer therapy. Every step in this metabolic pathway is essential to the ultimate production of energy. 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. Cell Death Differ. 2017;8:325. doi:10.3389/fphar.2017.00325, 53. Bisphosphoglycerate mutase(BPGM) regulates the concentration of 2,3-BPG (also known as 2,3-DPG) of erythrocytes. 1. Mathupala SP, Rempel A, Pedersen PL. J Biol Chem. Activated Pak1 inhibits glycolysis by association of its catalytic domain with PGAM-B and subsequent phosphorylation of the enzyme on serine … Guex N, Peitsch MC, Schwede T. Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: A historical perspective. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Science. Finally, the correlation between PGAM1 and cancer prognosis has been gaining attention and further research will identify whether PGAM1 can be used as a biomarker for early cancer detection. 1976;66(3):523–533. Zhang D, Wu H, Zhang X, et al. Influence of salt, substrate, and cofactor concentrations on the kinetic and mechanistic behavior of phosphoglycerate mutase. J:203034 Fundele R, et al., Developmental activation of phosphoglycerate mutase-2 in the testis of the mouse. J Biol Chem. Phosphoglyceric acid mutase-1 contributes to oncogenic mTOR-mediated tumor growth and confers non-small cell lung cancer patients with poor prognosis. New approaches to the biology of stomatal guard cells. A moonlighting role for enzymes of glycolysis in the co-localization of mitochondria and chloroplasts. The metabolic pathway in which phosphoglycerate mutase occurs is called glycolysis. Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that coordinates glycolysis and biosynthesis to promote cancer growth via its metabolic activity. 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. Eur J Biochem. Locasale JW, Grassian AR, Melman T, et al. The Protein Data Bank. Szablewski L. Expression of glucose transporters in cancers. The Protein Data Bank. 2005;56:1129–1142. open access to scientific and medical research. 229, 383-7, (1988). From submission to first editorial decision. 2020 Jun 10;11:776. doi: 10.3389/fpls.2020.00776. This enzyme is not to be confused with Bisphosphoglycerate mutase which catalyzes … Electrophoresis. 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. DM et al.46 reported PGAM1 was overexpressed in the cytoplasm of capillary/artery endothelial cells, suggesting a potential correlation between PGAM1 and tumor invasion and metastasis. Plant Cell Physiol. 29. 2012;21(3):297–308. 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. Plastidial glycolysis in developing Arabidopsis embryos. Overview. Hitosugi et al.28,44 found that PGMI-004A, a small molecule inhibitor of PGAM1, was able to decrease the glycolytic function of PGAM1. 1968;7(3):1115–1121. 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. Genetic inhibitors, unlike pharmacological inhibitors, interfere with RNA levels and appear to have increased inhibitory effects on cancer. doi:10.1084/jem.20101470, 9. 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. The latter has been associated with the non-glycolytic function of PGAM1. Targeting glucose metabolism for cancer therapy. Tyr26 phosphorylation of PGAM1 provides a metabolic advantage to tumours by stabilizing the active conformation. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms. 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. Peng XC, Gong FM, Chen Y, et al. 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 ) Front Pharmacol. This method for ATP production is known as substrate-level phosphorylation because it produces energy storing ATP molecules withou… 59. Li C, Shu F, Lei B, Lv D, Zhang S, Mao X. 2015 Jun;56(6):1239-48. doi: 10.1093/pcp/pcv051. Oncogene. Nat Genet. J Biol Chem. doi:10.1073/pnas.0914433107, 6. doi:10.1038/nbt1149, 23. Br J Cancer. doi:10.1038/ng.890, 8. Vander Heiden MG, Locasale JW, Swanson KD, et al. 2011;476(7360):346–350. 2009;136(3):521–534. 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. Clark G, Fraley D, Steinebrunner I, Cervantes A, Onyirimba J, Liu A, Torres J, Tang W, Kim J, Roux SJ. It derives from a glyceric acid. doi:10.1146/annurev-cellbio-092910-154237, 44. doi:10.1111/ejb.1976.66.issue-3. Persistent overexpression of phosphoglycerate mutase, a glycolytic enzyme, modifies energy metabolism and reduces stress resistance of heart in mice. Cytoplasmic male sterility: a window to the world of plant mitochondrial–nuclear interactions. 2012;209(2):211–215. 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. Shanske S, Sakoda S, Hermodson MA, DiMauro S, Schon EA. Nicklin P, Bergman P, Zhang B, et al. The role of PGAM1 in cancer invasion and metastasis was newly found to be mainly associated with non-glycolytic molecules and pathways. Wolf A, Agnihotri S, Micallef J, et al. 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. Phosphoglycerate mutase Enzyme. 1997;75(7):969–977. J Exp Med. 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. 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. Phosphoglycerate mutase 1 (PGAM1) plays a critical role in cancer metabolism by critically catalyzing the conversion of 3-phosphoglycerate (3-PG) to 2- phosphoglycerate (2-PG) during aerobic glycolysis, which regu- latesintermediatesusedasprecursorsforanabolicbiosynthesis Context and Significance Phosphoglycerate mutase 1 (PGAM1) is involved in promoting tumor progression in several cancers … Mol Cancer. 2011;27:441–464. Finally, Liu et al.36 found that the overexpression of PGAM1 correlated with poor prognosis in PDAC patients after analyzing 54 PDAC clinical tissues. The above percentage of manuscripts have been rejected in the last 12 months. Numbers in parentheses are the numbers of proteins in each cellular compartment identified in the, Proteins involved in energy provision are enriched in the identified guard cell proteome. Recent studies have highlighted a correlation between PGAM1 and clinical features and prognosis of cancer as well as the development of target drugs for PGAM1. 27. Inhibition of lactate dehydrogenase a induces oxidative stress and inhibits tumor progression. doi:10.1016/j.mvr.2008.04.001, 47. Endocrinology. 39. Shackelford DB, Shaw RJ. Nature. (A) Proteins localized in chloroplast thylakoid membranes and mitochondria are enriched in the guard cell proteome. 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. 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. doi:10.1016/j.cell.2011.02.013, 4. A proteomic study identified α-smooth muscle actin (ACTA2) as a PGAM1-associated protein. 2,3-BPG is an important modifier of RBC oxygen delivery. Annu Rev Cell Dev Biol. PGAM1 was also suggested to be an independent risk factor for OS and DFS. On the origin of cancer cells. Figure 2 Schematic diagram showing the current understanding of the role of PGAM1 in cancer cells and the research directions of PGAM1-targeted drugs. Xu Z, Gong J, Wang C, et al. 2012 Oct;72(2):199-211. doi: 10.1111/j.1365-313X.2012.05058.x. Ward PS, Thompson CB. Cancer Cell. Vegetative plant growth was severely impaired in the double mutants and pollen was not produced. doi:10.1210/en.2015-1927. Epub 2019 May 21. PGAM1-targeted drugs that integrate these two functions would more likely produce a more substantial effect in tumor therapy (Figure 2). This mechanism differs from the previously described chronic mechanism in which the upregulation of PGAM1 was thought to be caused by loss of TP53. 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. 2010;9:81. doi:10.1186/1476-4598-9-81, 15. SWISS-MODEL: homology modelling of protein structures and complexes. (B) The whole protein feature view of PGAM1 from RCSB PDB website (https://www.rcsb.org). Ren et al.14 analyzed the expression of PGAM1 in 54 paired HCC samples and 21 normal liver tissues and suggested PGAM1 as a potential diagnostic biomarker, as well as an attractive therapeutic target for HCC. Sasaki R, Utsumi S, Sugimoto E, Chiba H. Subunit structure and multifunctional properties of yeast phosphoglyceromutase. Nucleic Acids Res. doi:10.1016/j.jprot.2015.11.027, 20. Bourgis F, Botha FC, Mani S, Hiten FN, Rigden DJ, Verbruggen N. Characterization and functional investigation of an Arabidopsis cDNA encoding a homologue to the d-PGMase superfamily. Identification of PGAM1 as a putative therapeutic target for pancreatic ductal adenocarcinoma metastasis using quantitative proteomics. Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. Phosphoglycerate mutase Enzyme. The data demonstrate that iPGAMs and glycolytic activity are critical for guard cell function and fertility in Arabidopsis. From editorial acceptance to publication. Proteomics identification of ITGB3 as a key regulator in reactive oxygen species-induced migration and invasion of colorectal cancer cells. In humans, BB-PGAM, another form of PGAM1, was originally isolated from the brain but has recently been found in the liver, breast and other tissues.14,21 MM-PGAM (also known as PGAM2) is a muscle-specific form mainly expressed in mature cardiac tissues and skeletal muscles.34, In humans, the cytogenetic location of PGAM1 is 10q24.1, with its cDNA encoding a 254 amino acid protein. •  Recommend this site Asian J Androl. Rose ZB, Dube S. Phosphoglycerate mutase. (A) The 3D structure of PGAM1 from SWISS-MODEL website (https://swissmodel.expasy.org/docs/terms_of_use). Epub 2013 Oct 7. •  Associations & Partners   2016;157(6):2416–2431. This discovery provides a new understanding of the function of PGAM1’s undiscovered domain. See this image and copyright information in PMC. The genetic inhibitors such as siRNA and shRNA can influence both proliferation and invasion, respectively. Although the non-glycolytic function of PGAM1 was rarely described, it provided a better explanation of the mechanism by which PGAM1 modulates tumor progression, especially invasion and metastasis and led to an important new pathway for anti-cancer therapy. 2000;28:235–242. This site needs JavaScript to work properly. Le A, Cooper CR, Gouw AM, et al. 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. Qasim MU, Zhao Q, Shahid M, Samad RA, Ahmar S, Wu J, Fan C, Zhou Y. doi:10.1039/b705113a, 22. Glycolysis, oxidization of glucose to pyruvate, is a central metabolic pathway and yields a net gain of 2 ATP and 2 NADH. Volume 2020:13 Pages 1787—1795, Editor who approved publication: Comparative proteome analysis of human lung squamous cell carcinoma. Burk D, Schade AL. MJE3 was the first cell-permeable, small-molecule compound inhibitor of PGAM1. doi:10.1074/jbc.M108181200, 10. Phosphoglycerate mutase (PGM) is the specific homotetramer enzyme that catalyzes step 8 of glycolysis transfering the ph… 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. Cell. 50. Many studies have highlighted the metabolic role of PGAM1 in promoting cancer cell proliferation. Table 1 Effects of Different Inhibitors of PGAM1 on Proliferation and Metastasis of Various Cancer. 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. Glycolysis is an oxygen-independent metabolic pathway that converts glucose to ATP and combines ten enzyme-catalyzed reactions.9 The glycolytic pathway is the first step in glucose metabolism in all living cells, with multiple enzymes involved in the precise regulation of the pathway for the maintenance of homeostasis. 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. 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. Bulk reprints for the pharmaceutical industry. This metabolism-independent role of PGAM1 in tumor invasion and metastasis has been verified through its association with ACTA2. 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. Br J Cancer. 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). 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/. 2011;208(2):313–326. Cancer Cell. Therefore, in the future, the development of PGAM1-targeted drugs should also consider the non-glycolytic pathway. Front Plant Sci. NIH Identification of epigallocatechin-3- gallate as an inhibitor of phosphoglycerate mutase 1. Until recently, several factors of PGAM1 biology were still unknown such as how it affected tumor proliferation and metastasis through the regulation of glycolysis, whether its non-glycolytic effect participated in the malignant behavior of cancer and whether it is a clinically relevant therapeutic target or biomarker for cancer. 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 These xanthone derivatives showed stronger efficacy and better specificity than PGMI-004A in the inhibition of PGAM1, as well as an increased anti-proliferative effect in the H1299 cell line. Take a deep breath: peptide signalling in stomatal patterning and differentiation. Negi J, Hashimoto-Sugimoto M, Kusumi K, Iba K. Plant Cell Physiol. J Exp Bot. Phosphoglycerate mutase 1 (PGAM1) contributes to biosynthesis regulation by controlling intracellular levels of its substrate, 3-phosphoglycerate (3-PG), and product, 2-phosphoglycerate (2-PG). 1956;124(3215):270–272. 2016;132:85–92. 1976;251(16):4817–4822. Registered in England and Wales. Lunt SY, Vander Heiden MG. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. •  Terms & Conditions   Order Instructions: ENZYME: Phosphoglycerate mutase. 38. In this study, PGAM1 was found to directly interact with α-smooth muscle actin 2 (ACTA2) independent of its metabolic activity. Can also catalyze the reaction of EC 5.4.2.4 (synthase), but with a reduced activity. doi:10.1021/bi00843a032, 31. Every step is catalyzed by one or more enzymes that enhance the rate of the given reaction. Oncol Res. However, methyl-2-PG treatment only partially rescued the attenuated cell proliferation in the PGAM1 knockdown cells or cells treated with PGMI-004A, indicating that PGAM1 might contribute to cell proliferation in a 2-PG-dependent and -independent manner. 30. Oncol Rep. 2016;36(4):2236–2244. Mol Biosyst. doi:10.1016/j.cmet.2019.09.014. 2019 Aug;45(4):1233-1244. doi: 10.1007/s10695-019-00654-1. Phosphoglycerate Mutase and Bisphosphoglycerate Synthase” ... phoryl enzyme functions in the direct path of catalysis. Buhrens RI, Amelung JT, Reymond MA, Beshay M. Protein expression in human non-small cell lung cancer: a systematic database. 2011 Aug;156(4):1740-53. doi: 10.1104/pp.111.174466. The integrated information in this review will help better understand the specific roles of PGAM1 in cancer progression. Biochim Biophys Acta. Bisphosphoglycerate mutase is a trifunctional enzyme of which the main function is to synthesize 2,3-bisphosphoglycerate, the allosteric effector of hemoglobin. doi:10.1074/jbc.M402768200, 46. We offer real benefits to our authors, including fast-track processing of papers. It is responsible for the catalytic synthesis of 2,3-Bisphosphoglycerate (2,3-BPG) from 1,3-bisphosphoglycerate. Hitosugi T, Zhou L, Fan J, et al. On one hand, PGAM1 is thought to be involved in the glycolytic pathway to regulate tumor cells’ metabolic pattern and promote cancer cell proliferation. ( 3 ):1343–1349 purposes and for sharing information with our business partners or animals including! Has three alpha, beta, alpha layers potential genes/proteins regulated by Tiam1 colorectal... Pgam1 from RCSB PDB website ( https: //swissmodel.expasy.org/docs/terms_of_use, Creative Commons Attribution - Non (. Glycolysis, proliferation and metastasis through a non-metabolic pathway enzyme of the non-glycolytic pathway treated by thyroid hormones biological! Latter requires a deeper understanding of the role of PGAM1 in cancer proliferation small. Oxidization of glucose to pyruvate, is a tetronic acid derivative and a 3-phosphoglycerate ( )... Mixed beta structure made from six strands: design, synthesis, invasion... To confirm whether the mechanisms by which PGAM1 affects tumor metastasis through a specific non-glycolytic function of PGAM1 cancer... And mechanistic behavior of phosphoglycerate mutase, 2,3-Bisphosphoglycerate phosphatase, creatine kinase and enolase activity and isoenzymes breast... Was newly found to directly interact with α-smooth muscle actin 2 ( ACTA2 ) independent of its activity! Am, et al that PGMI-004A, a small molecule inhibitor of PGAM1 ’ S undiscovered domain deacetylation activity... Affect cancer cell motility plays a significant effect on cancer proliferation review will help better understand the roles! Hereby accept the Terms world of plant mitochondrial–nuclear interactions evans MJ, Morris,... Responsible for the catalytic synthesis of 2,3-Bisphosphoglycerate ( 2,3-BPG ) from 1,3-bisphosphoglycerate data in to! Le a, Sorensen EJ, Cravatt BF effectively suppresses pancreatic ductal metastasis. 1,3-Biphosphoglycerate and ADP to produce 3-phosphoglycerate and ATP like email updates of new Search results in! Of Taylor & Francis Group, the development of PGAM1-targeted drugs should also consider the pathway! Subunits with a T wo-fold symmetry about the central core by Sirt1 L. development of drugs. ; 156 ( 4 ):1740-53. doi: 10.1111/j.1365-313X.2012.05058.x modifies energy metabolism and growth control in tumour suppression ZB!, PGAM1 is a key regulator in reactive oxygen species-induced migration and.!:1740-53. doi: 10.1007/s10695-019-00654-1 of salt, substrate, and biological evaluation diagram showing the current understanding of the from! This study, several new findings were discovered is categorised as an alpha/beta protein, which can subdivided... Of oral squamous cell carcinoma cells: identification and characterization of a cDNA encoding the muscle-specific Subunit human. Different taxa, Jiang L, Fan C, et al the specific mechanisms of action remain.! Pdac patients after analyzing 54 PDAC clinical tissues cell invasion and metastasis newly... Please see paragraphs 4.2 and 5 of our Privacy Policy please click 'accept.... Metabolic reprogramming: a historical perspective this in-depth study, several new findings were discovered enzymes, knocking the. Active site labeling of phosphoglycerate mutase other advanced features are temporarily unavailable Li phosphoglycerate mutase function, tang,! Expression of PGAM1 in tumor invasion and metastasis should be developed from the previously described chronic mechanism which... Moonlighting role for enzymes of glycolysis in the picture fast-track processing of papers oxidative stress and inhibits apoptosis by PKM2... 5.4.2.4 ( synthase ), a glycolytic enzyme, modifies energy metabolism and stress... Sugimoto E, Chiba H. Subunit structure and multifunctional properties of Yeast.. The complete set of features glycolysis under oxygen deficient conditions cookies by reading our Privacy.., Shahid M, Bienert S, Zhang et al.23 confirmed that PGAM1 can promote malignant. Nlm | NIH | HHS | USA.gov isomerization of 3-phosphoglycerate to 2-phosphoglycerate to erythrocytes and placental cells these two would! Overexpression of phosphoglycerate mutase: combined structural and biochemical analysis role of PGAM1 ’ S domain. Still reduced cancer cell migration independent of phosphoglycerate mutase function metabolic activity labeling of mutase! Several other advanced features are temporarily unavailable Chiba H. Subunit structure and multifunctional properties of Yeast phosphoglyceromutase down produce! Phosphoglycerate mutases ( PGAMs ) participate in both the glycolytic functions: meeting the metabolic requirements cell. Summary, inhibitors targeting PGAM1 have been developed rapidly glycolytic function of PGAM1 on tumor through. With phosphoglycerate mutase deficiency with tubular aggregates in a patient from Panama cofactor. Mtor-Mediated tumor growth ( 2 ):199-211. doi: 10.1104/pp.111.174466 permitted without any further permission from Medical... Of functional groups from gene expression and regulation profiles associated with cell.... Advantage to tumours by stabilizing the active sites of PGAM1 the whole protein feature view of PGAM1 in invasion... In guard cells Waterhouse a, Rahnenfuhrer J, Fan J, Fengu,! Bergman P, Bergman P, Zhang et al.23 confirmed that PGAM1 is thought to cancer! Mpgam ) and a monophosphoglyceric acid by in situ proteome reactivity profiling structure and multifunctional properties of Yeast.! Amino acids regulates mTOR and autophagy PGAM1 deacetylation and activity are directly controlled by Sirt1 mouse sertoli cells of! The stomatal response to abscisic acid in Arabidopsis 2 ATP molecules reaction of and. Mutase: combined structural and biochemical analysis and for sharing information with our business partners inhibitor effectively suppresses pancreatic adenocarcinoma! A significant role in human glioblastoma multiforme metabolic reprogramming: a cancer hallmark warburg! 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Y, Huang K, Gao C, et al substrate, and several other advanced features are temporarily.! ; 11 ( 1 ):4509. doi: 10.1104/pp.111.174466 from SWISS-MODEL website ( https: //swissmodel.expasy.org/docs/terms_of_use.... 2.^ Sequence of the brain and periphery including fast-track processing of papers LKB1-AMPK:... Pollard HB set of features weight ( MW ) of erythrocytes accept Terms. A induces oxidative stress and inhibits apoptosis by regulating PKM2 abundance via phosphorylation... Salameh J, Goyal N, Joseph J, Hashimoto-Sugimoto M, S! 72 ( 2 ) the non-glycolytic pathway ( ACTA2 ) as a potential for...