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Escherichia coli K-12 substr. MG1655 Enzyme: methylglyoxal synthase

Gene: mgsA Accession Numbers: G6497 (EcoCyc), b0963, ECK0954

Synonyms: mgs, yccG

Regulation Summary Diagram

Regulation summary diagram for mgsA

Subunit composition of methylglyoxal synthase = [MgsA]6
         methylglyoxal synthase = MgsA

Methylglyoxal synthase (MGS) catalyzes the apparently irreversible formation of methylglyoxal from dihydroxyacetone phosphate, an intermediate of glycolysis I (from glucose 6-phosphate). Methylglyoxal is extremely toxic to the cell, so the presence of methylglyoxal synthase in the organism seems at first paradoxical. The primary role of MGS appears to be the limitation of the accumulation of phosphorylated sugars, providing a bypass pathway for triose phosphate metabolism under conditions where levels of inorganic phosphate are inadequate. The enzyme is not present in abundance and the rate of methylglyoxal synthesis can be maintained at a relatively non-toxic level while still reducing the stress associated with the accumulation of sugar phosphates. Inorganic phosphate is a strong inhibitor [Totemeyer98].

A reaction mechanism involving initial deprotonation to the enol form of methylglyoxal has been proposed [Summers77]. Further studies on the reaction mechanism of the enzyme involved site-directed mutagenesis of predicted active site residues and kinetic characterization of the mutant enzymes [Saadat98] as well as X-ray crystallography and NMR spectroscopy [Saadat00, Marks01, Marks04].

Although gel filtration shows a molecular weight of 67 kDa for MGS [Hopper72], suggesting that the enzyme is a tetramer in solution, the crystal structure shows it to be a homohexamer [Saadat99]. Additional crystal structures of the enzyme in complex with various inhibitors have been solved [Saadat00, Marks01, Marks04].

An mgsA null mutant has no obvious growth defect under most conditions; of the tested conditions, only growth on xylose in the presence of cAMP resulted in growth inhibition. Overexpression of mgsA has no effect on growth in complex medium; however, growth on xylose, arabinose or glycerol as the sole source of carbon is inhibited [Totemeyer98].

Reviews: [Cooper84, Ferguson98a, Booth03]

Locations: cytosol

Map Position: [1,025,780 <- 1,026,238] (22.11 centisomes, 80°)
Length: 459 bp / 152 aa

Molecular Weight of Polypeptide: 16.919 kD (from nucleotide sequence), 17.0 kD (experimental) [Totemeyer98]

Molecular Weight of Multimer: 67.0 kD (experimental) [Hopper72]

Unification Links: ASAP:ABE-0003259, DIP:DIP-48252N, EchoBASE:EB2213, EcoGene:EG12307, EcoliWiki:b0963, ModBase:P0A731, OU-Microarray:b0963, PortEco:mgsA, PR:PRO_000023226, Protein Model Portal:P0A731, RefSeq:NP_415483, RegulonDB:G6497, SMR:P0A731, String:511145.b0963, UniProt:P0A731

Relationship Links: InterPro:IN-FAMILY:IPR004363, InterPro:IN-FAMILY:IPR011607, InterPro:IN-FAMILY:IPR018148, PDB:Structure:1B93, PDB:Structure:1EGH, PDB:Structure:1IK4, PDB:Structure:1S89, PDB:Structure:1S8A, Pfam:IN-FAMILY:PF02142, Prosite:IN-FAMILY:PS01335, Smart:IN-FAMILY:SM00851

Gene-Reaction Schematic

Gene-Reaction Schematic

GO Terms:
Biological Process:
Inferred from experimentInferred by computational analysisGO:0019242 - methylglyoxal biosynthetic process [GOA06, GOA01a, Kim04c]
Molecular Function:
Inferred from experimentInferred by computational analysisGO:0008929 - methylglyoxal synthase activity [GOA06, GOA01, GOA01a, Hopper72]
Inferred by computational analysisGO:0016829 - lyase activity [UniProtGOA11a]
Cellular Component:
Inferred from experimentInferred by computational analysisGO:0005829 - cytosol [DiazMejia09, Ishihama08, LopezCampistrou05]
Inferred by computational analysisGO:0005737 - cytoplasm [UniProtGOA11, UniProtGOA11a]

MultiFun Terms: metabolismcentral intermediary metabolismmethylglyoxal metabolism

Essentiality data for mgsA knockouts:

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB LennoxYes 37 Aerobic 7   Yes [Baba06, Comment 1]
M9 medium with 1% glycerolYes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 2]
MOPS medium with 0.4% glucoseYes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 1]
Yes [Feist07, Comment 3]

Last-Curated 03-Jun-2009 by Keseler I, SRI International

Enzymatic reaction of: methylglyoxal synthase

Inferred from experiment

Synonyms: glycerone-phosphate phospho-lyase

EC Number:

glycerone phosphate → methylglyoxal + phosphate

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction in which it was curated.

The reaction is irreversible in the direction shown. [Hopper71]

Activators (Unknown Mechanism): glycerone phosphate [Comment 4] Inhibitors (Allosteric): phosphate [Saadat98, Hopper71, Hopper72] Inhibitors (Competitive): phosphoglycolohydroxamate [Marks01], diphosphate [Hopper71, Hopper72, Comment 5], 2-phosphoglycolate [Saadat98] Inhibitors (Unknown Mechanism): arsenate [Hopper72, Comment 6], phosphoenolpyruvate [Hopper71, Comment 6], 3-phospho-D-glycerate [Hopper71, Hopper72, Comment 6]

Primary Physiological Regulators of Enzyme Activity: phosphoenolpyruvate, 3-phospho-D-glycerate, phosphate, diphosphate

Kinetic Parameters:
Substrate Km (μM) kcat (sec-1) Citations
glycerone phosphate 470.0 [Hopper72, BRENDA14]
glycerone phosphate 500.0 [Hopper71, BRENDA14]
glycerone phosphate 200.0 [Saadat98, BRENDA14]
glycerone phosphate 620.0, 200.0 179.0, 220.0 [Marks04, BRENDA14]

pH(opt): 6.3 [BRENDA14, Marks04], 6.8 [BRENDA14, Marks04], 7.5 [Hopper72]

Sequence Features

Protein sequence of methylglyoxal synthase with features indicated

Feature Class Location Citations Comment
Sequence-Conflict 1 -> 2
Inferred by curator[Wood89, UniProt15]
UniProt: (in Ref. 1; J04726).
Pfam PF02142 26 -> 118
Inferred by computational analysis[Finn14]
MGS : MGS-like domain
Active-Site 71
Author statement[UniProt15]

Gene Local Context (not to scale -- see Genome Browser for correct scale)

Gene local context diagram

Transcription Unit

Transcription-unit diagram


Peter D. Karp on Wed Jan 18, 2006:
Gene right-end position adjusted based on analysis performed in the 2005 E. coli annotation update [Riley06].
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Booth03: Booth IR, Ferguson GP, Miller S, Li C, Gunasekera B, Kinghorn S (2003). "Bacterial production of methylglyoxal: a survival strategy or death by misadventure?." Biochem Soc Trans 31(Pt 6);1406-8. PMID: 14641075

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Cooper70: Cooper RA, Anderson A (1970). "The formation and catabolism of methylglyoxal during glycolysis in Escherichia coli." FEBS Lett 11(4);273-276. PMID: 11945504

Cooper84: Cooper RA (1984). "Metabolism of methylglyoxal in microorganisms." Annu Rev Microbiol 1984;38;49-68. PMID: 6093685

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Ferguson98a: Ferguson GP, Totemeyer S, MacLean MJ, Booth IR (1998). "Methylglyoxal production in bacteria: suicide or survival?." Arch Microbiol 170(4);209-18. PMID: 9732434

Finn14: Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, Sonnhammer EL, Tate J, Punta M (2014). "Pfam: the protein families database." Nucleic Acids Res 42(Database issue);D222-30. PMID: 24288371

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Hopper71: Hopper DJ, Cooper RA (1971). "The regulation of Escherichia coli methylglyoxal synthase; a new control site in glycolysis?." FEBS Lett 13(4);213-216. PMID: 11945670

Hopper72: Hopper DJ, Cooper RA (1972). "The purification and properties of Escherichia coli methylglyoxal synthase." Biochem J 1972;128(2);321-9. PMID: 4563643

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Kim04c: Kim I, Kim E, Yoo S, Shin D, Min B, Song J, Park C (2004). "Ribose utilization with an excess of mutarotase causes cell death due to accumulation of methylglyoxal." J Bacteriol 186(21);7229-35. PMID: 15489434

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

Marks01: Marks GT, Harris TK, Massiah MA, Mildvan AS, Harrison DH (2001). "Mechanistic implications of methylglyoxal synthase complexed with phosphoglycolohydroxamic acid as observed by X-ray crystallography and NMR spectroscopy." Biochemistry 40(23);6805-18. PMID: 11389594

Marks04: Marks GT, Susler M, Harrison DH (2004). "Mutagenic studies on histidine 98 of methylglyoxal synthase: effects on mechanism and conformational change." Biochemistry 43(13);3802-13. PMID: 15049687

Riley06: Riley M, Abe T, Arnaud MB, Berlyn MK, Blattner FR, Chaudhuri RR, Glasner JD, Horiuchi T, Keseler IM, Kosuge T, Mori H, Perna NT, Plunkett G, Rudd KE, Serres MH, Thomas GH, Thomson NR, Wishart D, Wanner BL (2006). "Escherichia coli K-12: a cooperatively developed annotation snapshot--2005." Nucleic Acids Res 34(1);1-9. PMID: 16397293

Saadat00: Saadat D, Harrison DH (2000). "Mirroring perfection: the structure of methylglyoxal synthase complexed with the competitive inhibitor 2-phosphoglycolate." Biochemistry 39(11);2950-60. PMID: 10715115

Saadat98: Saadat D, Harrison DH (1998). "Identification of catalytic bases in the active site of Escherichia coli methylglyoxal synthase: cloning, expression, and functional characterization of conserved aspartic acid residues." Biochemistry 1998;37(28);10074-86. PMID: 9665712

Saadat99: Saadat D, Harrison DH (1999). "The crystal structure of methylglyoxal synthase from Escherichia coli." Structure Fold Des 1999;7(3);309-17. PMID: 10368300

Summers77: Summers MC, Rose IA (1977). "Proton transfer reactions of methylglyoxal synthase." J Am Chem Soc 99(13);4475-8. PMID: 325056

Totemeyer98: Totemeyer S, Booth NA, Nichols WW, Dunbar B, Booth IR (1998). "From famine to feast: the role of methylglyoxal production in Escherichia coli." Mol Microbiol 1998;27(3);553-62. PMID: 9489667

UniProt15: UniProt Consortium (2015). "UniProt version 2015-08 released on 2015-07-22." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Wood89: Wood ER, Matson SW (1989). "The molecular cloning of the gene encoding the Escherichia coli 75-kDa helicase and the determination of its nucleotide sequence and gentic map position." J Biol Chem 264(14);8297-303. PMID: 2542273

Other References Related to Gene Regulation

MendozaVargas09: Mendoza-Vargas A, Olvera L, Olvera M, Grande R, Vega-Alvarado L, Taboada B, Jimenez-Jacinto V, Salgado H, Juarez K, Contreras-Moreira B, Huerta AM, Collado-Vides J, Morett E (2009). "Genome-wide identification of transcription start sites, promoters and transcription factor binding sites in E. coli." PLoS One 4(10);e7526. PMID: 19838305

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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