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Search The CSA
PDB ID
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EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1mbb

E.C. nameUDP-N-acetylmuramate dehydrogenase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 1.1.1.158
CSA Homologues of 1mbb1hsk,1mbr,1mbt,1uxy,2mbr,2q85,3i99,
CSA Entries With UniProtID P08373
CSA Entries With EC Number 1.1.1.158
PDBe Entry 1mbb
PDBSum Entry 1mbb
MACiE Entry M0353

Literature Report

IntroductionUridine diphospho-n-acetylenolpyruvylglucosamine reductase (MurB) from E. Coli reduces UDP-N-acetylenolpyruvylglucosamine to UDP-N-acetylmuramic acid. MurB is essential for the viability of bacterial cells. The absence of a homologue in eukaryotic cells makes MurB an attractive target for small molecule inhibitors with the potential to have broad antibacterial activity.
MechansimThe mechanism proceeds as follows: NADPH binds to the enzyme and hydride transfer of the 4-pro -S hydrogen of NADPH to N5 of an enzyme-bound flavin (FAD cofactor). Release of NADP+ is followed by the binding of UDP-GlcNAc to the enzyme active site. Hydride transfer from the reduced flavin to C3 of the enolpyruvyl moiety of the UDP-sugar substrate generates a carbanion equivalent at C2, which can be stabilized by the R -carboxylate at C1 as an enol intermediate. A proton from Ser229 is then transferred to C2, giving the UDPMurNAc product.
Reaction

Catalytic Sites for 1mbb

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerA229229macie:sideChainActs as a general acid to quench the enol intermediate to form the acid product.
GluA325325macie:sideChainActs to stabilise carbanion intermediate as an enol by hydrogen-bonding.
ArgA159159macie:sideChainActs to stabilise carbanion intermediate as an enol by hydrogen-bonding.

Literature References

Notes:
Lees WJ
(E)-enolbutyryl-UDP-N-acetylglucosamine as a mechanistic probe of UDP-N-acetylenolpyruvylglucosamine reductase (MurB).
Biochemistry 1996 35 1342-1351
PubMed: 8634262
Benson TE
Kinetic characterization of wild-type and S229A mutant MurB: evidence for the role of Ser 229 as a general acid.
Biochemistry 1997 36 796-805
PubMed: 9020777
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