|Gene:||mgsA||Accession Numbers: G6497 (EcoCyc), b0963, ECK0954|
Synonyms: mgs, yccG
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].
|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
|Biological Process:||GO:0019242 - methylglyoxal biosynthetic process [GOA06, GOA01a, Kim04f]|
|Molecular Function:||GO:0008929 - methylglyoxal synthase activity
[GOA06, GOA01, GOA01a, Hopper72]
GO:0016829 - lyase activity [UniProtGOA11a]
|Cellular Component:||GO:0005829 - cytosol
[DiazMejia09, Ishihama08, LopezCampistrou05]
GO:0005737 - cytoplasm [UniProtGOA11, UniProtGOA11a]
|MultiFun Terms:||metabolism → central intermediary metabolism → methylglyoxal metabolism|
|Growth Medium||Growth?||T (°C)||O2||pH||Osm/L||Growth Observations|
|LB Lennox||Yes||37||Aerobic||7||Yes [Baba06, Comment 1]|
|M9 medium with 1% glycerol||Yes||37||Aerobic||7.2||0.35||Yes [Joyce06, Comment 2]|
|MOPS medium with 0.4% glucose||Yes||37||Aerobic||7.2||0.22||Yes [Baba06, Comment 1] |
Yes [Feist07, Comment 3]
Enzymatic reaction of: methylglyoxal synthase
Synonyms: glycerone-phosphate phospho-lyase
EC Number: 18.104.22.168
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.
The reaction is irreversible in the direction shown. [Hopper71]
|Sequence-Conflict||1 -> 2|
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
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
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
Kim04f: 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
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
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
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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