spacer
View the latest EBI news stories and important announcements...
more

spacer
Search The CSA
PDB ID
UNIPROT ID
EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1b93

E.C. namemethylglyoxal synthase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 4.2.3.3
CSA Homologues of 1b931egh,1ik4,1s89,1s8a,1vmd,1wo8,
CSA Entries With UniProtID P0A731
CSA Entries With EC Number 4.2.3.3
PDBe Entry 1b93
PDBSum Entry 1b93
MACiE Entry M0085

Literature Report

IntroductionMethylglyoxyl synthase catalyses the first reaction in the methylglyoxyl bypass of the Embden-Myerhoff pathway (glycolysis), the conversion of dihydroxyacetone phosphate into methylglyoxal and orthophosphate. The physiological benefits of this are yet to be understood as the final product of methylglyoxal synthase is cytotoxic in small quantities and has been shown to be mutagenic and to interfere with de novo protein and nucleic acid synthesis. The intermediate, D-lactoylglutathione is also toxic in millimolar quantities, interfering with intermediate filament synthesis. The methylglyoxyl bypass system is inhibited allosterically by phosphate suggesting that is only functions in times of phosphate deprivation although more recent data imply that it may facilitate the transition between conditions of high and low phosphate. There is much interest in this enzyme for two reasons: firstly it has been implicated in diabetic complications and secondly due to its ability to metabolise anti-cancer drugs rendering treatments ineffective.
MechansimThe first step of the reaction mechanism involves the stereospecific abstraction of the C3 hydrogen of the substrate to form a common enediol enzyme intermediate. Asp71 abstracts a proton from the substrate whilst His98 protonates the ene-diol. His19 then abstracts the hydroxyl proton to initiate the phosphate elimination. Numerous other ligands stabilise intermediates formed in the active site.
Reaction

Catalytic Sites for 1b93

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA9898macie:sideChain
AspA7171macie:sideChain
HisA1919macie:sideChain
AspA101101macie:sideChain
AspA9191macie:sideChain
GlyA6666macie:mainChainAmide

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisB9898macie:sideChain
AspB7171macie:sideChain
HisB1919macie:sideChain
AspB101101macie:sideChain
AspB9191macie:sideChain
GlyB6666macie:mainChainAmide

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisC9898macie:sideChain
AspC7171macie:sideChain
HisC1919macie:sideChain
AspC101101macie:sideChain
AspC9191macie:sideChain
GlyC6666macie:mainChainAmide

Literature References

Notes:
Saadat D
Mirroring perfection: the structure of methylglyoxal synthase complexed with the competitive inhibitor 2-phosphoglycolate.
Biochemistry 2000 39 2950-2960
PubMed: 10715115
Saadat D
The crystal structure of methylglyoxal synthase from Escherichia coli.
Structure 1999 7 309-317
PubMed: 10368300
spacer
spacer