Phosphoglycerate kinase - wikipedia Phosphoglycerate kinase Phosphoglycerate kinase Identifiers EC number 2.7. 2.3 CAS number 9001 - 83 - 6 Databases IntEnz IntEnz view BRENDA BRENDA entry ExPASy NiceZyme view KEGG KEGG entry MetaCyc metabolic pathway PRIAM profile PDB structures RCSB PDB PDBe PDBsum Gene Ontology AmiGO / QuickGO Search PMC articles PubMed articles NCBI proteins Phosphoglycerate kinase Structure of yeast phosphoglycerate kinase. Identifiers Symbol PGK Pfam PF00162 InterPro IPR001576 PROSITE PDOC00102 SCOP 3pgk SUPERFAMILY 3pgk Available protein structures : Pfam structures PDB RCSB PDB ; PDBe ; PDBj PDBsum structure summary Phosphoglycerate kinase ( EC 2.7. 2.3 ) ( PGK 1 ) is an enzyme that catalyzes the reversible transfer of a phosphate group from 1, 3 - bisphosphoglycerate ( 1, 3 - BPG ) to ADP producing 3 - phosphoglycerate ( 3 - PG ) and ATP : 1, 3 - bisphosphoglycerate + ADP ⇌ glycerate 3 - phosphate + ATP Like all kinases it is a transferase. PGK is a major enzyme used in glycolysis, in the first ATP - generating step of the glycolytic pathway. In gluconeogenesis, the reaction catalyzed by PGK proceeds in the opposite direction, generating ADP and 1, 3 - BPG. In humans, two isozymes of PGK have been so far identified, PGK1 and PGK2. The isozymes have 87 - 88 % identical amino acid sequence identity and though they are structurally and functionally similar, they have different localizations : PGK2, encoded by an autosomal gene, is unique to meiotic and postmeiotic spermatogenic cells, while PGK1, encoded on the X-chromosome, is ubiquitously expressed in all cells. Contents 1 Biological function 1.1 Interactive pathway map 2 Structure 2.1 Overview 2.2 Role of magnesium 3 Mechanism 4 Regulation 5 Disease relevance 6 Human isozymes 7 References 8 External links Biological function Diagram showing glycolytic and gluconeogenic pathways. Note that phosphoglycerate kinase is used in both directions. PGK is present in all living organisms as one of the two ATP - generating enzymes in glycolysis. In the gluconeogenic pathway, PGK catalyzes the reverse reaction. Under biochemical standard conditions, the glycolytic direction is favored. In the Calvin cycle in photosynthetic organisms, PGK catalyzes the phosphorylation of 3 - PG, producing 1, 3 - BPG and ADP, as part of the reactions that regenerate ribulose - 1, 5 - bisphosphate. PGK has been reported to exhibit thiol reductase activity on plasmin, leading to angiostatin formation, which inhibits angiogenesis and tumor growth. The enzyme was also shown to participate in DNA replication and repair in mammal cell nuclei. The human isozyme PGK2, which is only expressed during spermatogenesis, was shown to be essential for sperm function in mice. Interactive pathway map Click on genes, proteins and metabolites below to link to respective articles. 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The enzyme exists as a 415 - residue monomer containing two nearly equal - sized domains that correspond to the N - and C - termini of the protein. 3 - phosphoglycerate ( 3 - PG ) binds to the N - terminal, while the nucleotide substrates, MgATP or MgADP, bind to the C - terminal domain of the enzyme. This extended two - domain structure is associated with large - scale ' hinge - bending ' conformational changes, similar to those found in hexokinase. The two domains of the protein are separated by a cleft and linked by two alpha - helices. At the core of each domain is a 6 - stranded parallel beta - sheet surrounded by alpha helices. The two lobes are capable of folding independently, consistent with the presence of intermediates on the folding pathway with a single domain folded. Though the binding of either substrate triggers a conformational change, only through the binding of both substrates does domain closure occur, leading to the transfer of the phosphate group. The enzyme has a tendency to exist in the open conformation with short periods of closure and catalysis, which allow for rapid diffusion of substrate and products through the binding sites ; the open conformation of PGK is more conformationally stable due to the exposure of a hydrophobic region of the protein upon domain closure. Role of magnesium Magnesium ions are normally complexed to the phosphate groups the nucleotide substrates of PGK. It is known that in the absence of magnesium, no enzyme activity occurs. The bivalent metal assists the enzyme ligands in shielding the bound phosphate group 's negative charges, allowing the nucleophilic attack to occur ; this charge - stabilization is a typical characteristic of phosphotransfer reaction. It is theorized that the ion may also encourage domain closure when PGK has bound both substrates. Mechanism Phosphoglycerate kinase mechanism in glycolysis. Without either substrate bound, PGK exists in an `` open '' conformation. After both the triose and nucleotide substrates are bound to the N - and C - terminal domains, respectively, an extensive hinge - bending motion occurs, bringing the domains and their bound substrates into close proximity and leading to a `` closed '' conformation. Then, in the case of the forward glycolytic reaction, the beta - phosphate of ADP initiates a nucleophilic attack on the 1 - phosphate of 1, 3 - BPG. The Lys219 on the enzyme guides the phosphate group to the substrate. PGK proceeds through a charge - stabilized transition state that is favored over the arrangement of the bound substrate in the closed enzyme because in the transition state, all three phosphate oxygens are stabilized by ligands, as opposed to only two stabilized oxygens in the initial bound state. In the glycolytic pathyway, 1, 3 - BPG is the phosphate donor and has a high phosphoryl - transfer potential. The PGK - catalyzed transfer of the phosphate group from 1, 3 - BPG to ADP to yield ATP can power the carbon - oxidation reaction of the previous glycolytic step ( converting glyceraldehyde 3 - phosphate to 3 - phosphoglycerate ). Regulation The enzyme is activated by low concentrations of various multivalent anions, such as pyrophosphate, sulfate, phosphate, and citrate. High concentrations of MgATP and 3 - PG activates PGK, while Mg2+ at high concentrations non-competitively inhibits the enzyme. PGK exhibits a wide specificity toward nucleotide substrates. Its activity is inhibited by salicylates, which appear to mimic the enzyme 's nucleotide substrate. Macromolecular crowding has been shown to increase PGK activity in both computer simluations and in vitro environments simulating a cell interior ; as a result of crowding, the enzyme becomes more enyzmatically active and more compact. Disease relevance Phosphoglycerate kinase ( PGK ) deficiency is an X-linked recessive trait associated with hemolytic anemia, mental disorders and myopathy in humans, depending on form -- there exists a hemolytic form and a myopathic form. Since the trait is X-linked, it is usually fully expressed in males, who have one X chromosome ; affected females are typically asymptomatic. The condition results from mutations in Pgk1, the gene encoding PGK1, and twenty mutations have been identified. On a molecular level, the mutation in Pgk1 impairs the thermal stability and inhibits the catalytic activity of the enzyme. PGK is the only enzyme in the immediate glycolytic pathway encoded by an X-linked gene. In the case of hemolytic anemia, PGK deficiency occurs in the erythrocytes. Currently, no definitive treatment exists for PGK deficiency. PGK1 overexpression has been associated with gastric cancer and has been found to increase the invasiveness of gastric cancer cells in vitro. The enzyme is secreted by tumor cells and participates in the angiogenic process, leading to the release of angiostatin and the inhibition of tumor blood vessel growth. Due to its wide specificity towards nucleotide substrates, PGK is known to participate in the phosphorylation and activation of HIV antiretroviral drugs, which are nucleotide - based. Human isozymes phosphoglycerate kinase 1 Identifiers Symbol PGK1 Entrez 5230 HUGO 8896 OMIM 311800 RefSeq NM_000291 UniProt P00558 Other data EC number 2.7. 2.3 Locus Chr. X q13. 3 phosphoglycerate kinase 2 Identifiers Symbol PGK2 Entrez 5232 HUGO 8898 OMIM 172270 RefSeq NM_138733 UniProt P07205 Other data EC number 2.7. 2.3 Locus Chr. 6 p21 - q12 References ^ Jump up to : Watson HC, Walker NP, Shaw PJ, Bryant TN, Wendell PL, Fothergill LA, Perkins RE, Conroy SC, Dobson MJ, Tuite MF ( 1982 ). `` Sequence and structure of yeast phosphoglycerate kinase ''. The EMBO Journal. 1 ( 12 ) : 1635 -- 40. PMC 553262. PMID 6765200. ^ Jump up to : Chiarelli LR, Morera SM, Bianchi P, Fermo E, Zanella A, Galizzi A, Valentini G ( 2012 ). `` Molecular insights on pathogenic effects of mutations causing phosphoglycerate kinase deficiency ''. PLOS ONE. 7 ( 2 ) : e32065. doi : 10.1371 / journal. pone. 0032065. PMC 3279470. PMID 22348148. ^ Jump up to : Lay AJ, Jiang XM, Kisker O, Flynn E, Underwood A, Condron R, Hogg PJ ( December 2000 ). `` Phosphoglycerate kinase acts in tumour angiogenesis as a disulphide reductase ''. Nature. 408 ( 6814 ) : 869 -- 73. doi : 10.1038 / 35048596. PMID 11130727. Jump up ^ Danshina PV, Geyer CB, Dai Q, Goulding EH, Willis WD, Kitto GB, McCarrey JR, Eddy EM, O'Brien DA ( Jan 2010 ). `` Phosphoglycerate kinase 2 ( PGK2 ) is essential for sperm function and male fertility in mice ''. Biology of Reproduction. 82 ( 1 ) : 136 -- 45. doi : 10.1095 / biolreprod. 109.079699. PMC 2802118. PMID 19759366. ^ Jump up to : Dhar A, Samiotakis A, Ebbinghaus S, Nienhaus L, Homouz D, Gruebele M, Cheung MS ( October 2010 ). `` Structure, function, and folding of phosphoglycerate kinase are strongly perturbed by macromolecular crowding ''. Proceedings of the National Academy of Sciences of the United States of America. 107 ( 41 ) : 17586 -- 91. doi : 10.1073 / pnas. 1006760107. PMC 2955104. PMID 20921368. Jump up ^ Kumar S, Ma B, Tsai CJ, Wolfson H, Nussinov R ( 1999 ). `` Folding funnels and conformational transitions via hinge - bending motions ''. Cell Biochemistry and Biophysics. 31 ( 2 ) : 141 -- 64. doi : 10.1007 / BF02738169. PMID 10593256. ^ Jump up to : Yon JM, Desmadril M, Betton JM, Minard P, Ballery N, Missiakas D, Gaillard - Miran S, Perahia D, Mouawad L ( 1990 ). `` Flexibility and folding of phosphoglycerate kinase ''. Biochimie. 72 ( 6 - 7 ) : 417 -- 29. doi : 10.1016 / 0300 - 9084 ( 90 ) 90066 - p. PMID 2124145. Jump up ^ Zerrad L, Merli A, Schröder GF, Varga A, Gráczer É, Pernot P, Round A, Vas M, Bowler MW ( April 2011 ). `` A spring - loaded release mechanism regulates domain movement and catalysis in phosphoglycerate kinase ''. The Journal of Biological Chemistry. 286 ( 16 ) : 14040 -- 8. doi : 10.1074 / jbc. M110. 206813. PMC 3077604. PMID 21349853. ^ Jump up to : Varga A, Palmai Z, Gugolya Z, Gráczer É, Vonderviszt F, Závodszky P, Balog E, Vas M ( December 2012 ). `` Importance of aspartate residues in balancing the flexibility and fine - tuning the catalysis of human 3 - phosphoglycerate kinase ''. Biochemistry. 51 ( 51 ) : 10197 -- 207. doi : 10.1021 / bi301194t. PMID 23231058. Jump up ^ Cliff MJ, Bowler MW, Varga A, Marston JP, Szabó J, Hounslow AM, Baxter NJ, Blackburn GM, Vas M, Waltho JP ( May 2010 ). `` Transition state analogue structures of human phosphoglycerate kinase establish the importance of charge balance in catalysis ''. Journal of the American Chemical Society. 132 ( 18 ) : 6507 -- 16. doi : 10.1021 / ja100974t. PMID 20397725. Jump up ^ Banks, R.D. ; Blake, C.C.F. ; Evans, P.R. ; Haser, R. ; Rice, D.W. ; Hardy, G.W. ; Merrett, M. ; Phillips, A.W. ( 28 June 1979 ). `` Sequence, structure and activity of phosphoglycerate kinase : a possible hinge - bending enzyme ''. Nature. 279 ( 5716 ) : 773 -- 777. doi : 10.1038 / 279773a0. Jump up ^ Bernstein BE, Hol WG ( March 1998 ). `` Crystal structures of substrates and products bound to the phosphoglycerate kinase active site reveal the catalytic mechanism ''. Biochemistry. 37 ( 13 ) : 4429 -- 36. doi : 10.1021 / bi9724117. PMID 9521762. Jump up ^ Larsson - Raźnikiewicz M ( Jan 1967 ). `` Kinetic studies on the reaction catalyzed by phosphoglycerate kinase. II. The kinetic relationships between 3 - phosphoglycerate, MgATP2 - and activating metal ion ''. Biochimica et Biophysica Acta. 132 ( 1 ) : 33 -- 40. doi : 10.1016 / 0005 - 2744 ( 67 ) 90189 - 1. PMID 6030358. ^ Jump up to : Varga A, Chaloin L, Sági G, Sendula R, Gráczer E, Liliom K, Závodszky P, Lionne C, Vas M ( June 2011 ). `` Nucleotide promiscuity of 3 - phosphoglycerate kinase is in focus : implications for the design of better anti-HIV analogues ''. Molecular bioSystems. 7 ( 6 ) : 1863 -- 73. doi : 10.1039 / c1mb05051f. PMID 21505655. Jump up ^ Larsson - Raźnikiewicz, Märtha ; Wiksell, Eva ( 1 March 1978 ). `` Inhibition of phosphoglycerate kinase by salicylates ''. Biochimica et Biophysica Acta ( BBA ) - Enzymology. 523 ( 1 ) : 94 -- 100. doi : 10.1016 / 0005 - 2744 ( 78 ) 90012 - 8. Jump up ^ Yoshida A, Tani K ( 1983 ). `` Phosphoglycerate kinase abnormalities : functional, structural and genomic aspects ''. Biomedica Biochimica Acta. 42 ( 11 - 12 ) : S263 -- 7. PMID 6689547. ^ Jump up to : Beutler E ( Jan 2007 ). `` PGK deficiency ''. British Journal of Haematology. 136 ( 1 ) : 3 -- 11. doi : 10.1111 / j. 1365 - 2141.2006. 06351. x. PMID 17222195. Jump up ^ NIH Genetics Home Reference Jump up ^ Rhodes M, Ashford L, Manes B, Calder C, Domm J, Frangoul H ( February 2011 ). `` Bone marrow transplantation in phosphoglycerate kinase ( PGK ) deficiency ''. British Journal of Haematology. 152 ( 4 ) : 500 -- 2. doi : 10.1111 / j. 1365 - 2141.2010. 08474. x. PMID 21223252. Jump up ^ Zieker D, Königsrainer I, Tritschler I, Löffler M, Beckert S, Traub F, Nieselt K, Bühler S, Weller M, Gaedcke J, Taichman RS, Northoff H, Brücher BL, Königsrainer A ( March 2010 ). `` Phosphoglycerate kinase 1 a promoting enzyme for peritoneal dissemination in gastric cancer ''. International Journal of Cancer. 126 ( 6 ) : 1513 -- 20. doi : 10.1002 / ijc. 24835. PMC 2811232. PMID 19688824. Jump up ^ Gallois - Montbrun S, Faraj A, Seclaman E, Sommadossi JP, Deville - Bonne D, Véron M ( November 2004 ). `` Broad specificity of human phosphoglycerate kinase for antiviral nucleoside analogs ''. Biochemical Pharmacology. 68 ( 9 ) : 1749 -- 56. doi : 10.1016 / j. bcp. 2004.06. 012. PMID 15450940. External links Phosphoglycerate kinase at the US National Library of Medicine Medical Subject Headings ( MeSH ) Illustration at arizona.edu This article incorporates text from the public domain Pfam and InterPro IPR001576 Glycolysis metabolic pathway Glucose Hexokinase ATP ADP Glucose 6 - phosphate Glucose - 6 - phosphate isomerase Fructose 6 - phosphate phosphofructokinase - 1 ATP ADP Fructose 1, 6 - bisphosphate Fructose - bisphosphate aldolase Dihydroxyacetone phosphate + + Glyceraldehyde 3 - phosphate Triosephosphate isomerase 2 × Glyceraldehyde 3 - phosphate 2 × Glyceraldehyde - 3 - phosphate dehydrogenase NAD + P NADH + H NAD + P NADH + H 2 × 1, 3 - Bisphosphoglycerate 2 × Phosphoglycerate kinase ADP ATP ADP ATP 2 × 3 - Phosphoglycerate 2 × Phosphoglycerate mutase 2 × 2 - Phosphoglycerate 2 × Phosphopyruvate hydratase ( Enolase ) H O H O 2 × Phosphoenolpyruvate 2 × Pyruvate kinase ADP ATP 2 × Pyruvate 2 × Metabolism : carbohydrate metabolism : glycolysis / gluconeogenesis enzymes Glycolysis Hexokinase ( HK1, HK2, HK3, Glucokinase ) → / Glucose 6 - phosphatase ← Glucose isomerase Phosphofructokinase 1 ( Liver, Muscle, Platelet ) → / Fructose 1, 6 - bisphosphatase ← Fructose - bisphosphate aldolase ( Aldolase A, B, C ) Triosephosphate isomerase Glyceraldehyde 3 - phosphate dehydrogenase Phosphoglycerate kinase Phosphoglycerate mutase Enolase Pyruvate kinase ( PKLR, PKM2 ) Gluconeogenesis only to oxaloacetate : Pyruvate carboxylase Phosphoenolpyruvate carboxykinase from lactate ( Cori cycle ) : Lactate dehydrogenase from alanine ( Alanine cycle ) : Alanine transaminase from glycerol : Glycerol kinase Glycerol dehydrogenase Regulatory Fructose 6 - P, 2 - kinase : fructose 2, 6 - bisphosphatase PFKFB1, PFKFB2, PFKFB3, PFKFB4 Bisphosphoglycerate mutase Transferases : phosphorus - containing groups ( EC 2.7 ) 2.7. 1 - 2.7. 4 : phosphotransferase / kinase ( PO ) 2.7. 1 : OH acceptor Hexo - Gluco - Fructo - Hepatic Galacto - Phosphofructo - Liver Muscle Platelet Riboflavin Shikimate Thymidine ADP - thymidine NAD Glycerol Pantothenate Mevalonate Pyruvate Deoxycytidine PFP Diacylglycerol Phosphoinositide 3 Class I PI 3 Class II PI 3 Sphingosine Glucose - 1, 6 - bisphosphate synthase 2.7. 2 : COOH acceptor Phosphoglycerate Aspartate kinase 2.7. 3 : N acceptor Creatine 2.7. 4 : PO acceptor Phosphomevalonate Adenylate Nucleoside - diphosphate Uridylate Guanylate Thiamine - diphosphate 2.7. 6 : diphosphotransferase ( P O ) Ribose - phosphate diphosphokinase Thiamine diphosphokinase 2.7. 7 : nucleotidyltransferase ( PO - nucleoside ) Polymerase DNA polymerase DNA - directed DNA polymerase II III IV V RNA - directed DNA polymerase Reverse transcriptase Telomerase DNA nucleotidylexotransferase / Terminal deoxynucleotidyl transferase RNA nucleotidyltransferase RNA polymerase / DNA - directed RNA polymerase RNA polymerase I II III IV V Primase RNA - dependent RNA polymerase PNPase Phosphorolytic 3 ' to 5 ' exoribonuclease RNase PH PNPase Nucleotidyltransferase UTP -- glucose - 1 - phosphate uridylyltransferase Galactose - 1 - phosphate uridylyltransferase Guanylyltransferase mRNA capping enzyme Other Recombinase ( Integrase ) Transposase 2.7. 8 : miscellaneous Phosphatidyltransferases CDP - diacylglycerol -- glycerol - 3 - phosphate 3 - phosphatidyltransferase CDP - diacylglycerol -- serine O - phosphatidyltransferase CDP - diacylglycerol -- inositol 3 - phosphatidyltransferase CDP - diacylglycerol -- choline O - phosphatidyltransferase Glycosyl - 1 - phosphotransferase N - acetylglucosamine - 1 - phosphate transferase 2.7. 10 - 2.7. 13 : protein kinase ( PO ; protein acceptor ) 2.7. 10 : protein - tyrosine see tyrosine kinases 2.7. 11 : protein - serine / threonine see serine / threonine - specific protein kinases 2.7. 12 : protein - dual - specificity see serine / threonine - specific protein kinases 2.7. 13 : protein - histidine Protein - histidine pros - kinase Protein - histidine tele - kinase Histidine kinase Enzymes Activity Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Regulation Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator Classification EC number Enzyme superfamily Enzyme family List of enzymes Kinetics Enzyme kinetics Eadie -- Hofstee diagram Hanes -- Woolf plot Lineweaver -- Burk plot Michaelis -- Menten kinetics Types EC1 Oxidoreductases ( list ) EC2 Transferases ( list ) EC3 Hydrolases ( list ) EC4 Lyases ( list ) EC5 Isomerases ( list ) EC6 Ligases ( list ) Molecular and Cellular Biology portal Retrieved from `` https://en.wikipedia.org/w/index.php?title=Phosphoglycerate_kinase&oldid=818153106 '' Categories : Genes on human chromosome X Genes on human chromosome 6 Glycolysis EC 2.7. 2 Hidden categories : Protein pages needing a picture Use dmy dates from April 2017 Talk Search Contents About Wikipedia Deutsch Español Français Galego Italiano Polski Русский Српски / srpski Srpskohrvatski / српскохрватски Suomi 3 more Edit links This page was last edited on 1 January 2018, at 22 : 35. 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Question: phosphoglycerate kinase catalyzes the conversion of 1 3-bisphosphoglycerate to
Answer: ADP producing 3-phosphoglycerate (3-PG) and ATP