22.214.171.124 - UDP-N-acetylmuramate dehydrogenase
- UDP-GlcNAc-enoylpyruvate reductase.
- Uridine diphospho-N-acetylglucosamine-enolpyruvate reductase.
- UDP-N-acetylglucosamine-enoylpyruvate reductase.
- UDP-N-acetylenolpyruvoylglucosamine reductase.
- Uridine diphosphoacetylpyruvoylglucosamine reductase.
NADP(+) + UDP-N-acetyl-alpha-D-muramate = H(+) + NADPH + UDP-N-acetyl-3-O-(1-carboxyvinyl)-alpha-D-glucosamine
UDP-N-acetylenolpyruvylglucosamine reductase (MurB) reduces both E and Z isomers of enolbutyryl-UDP-GlcBAc analogs of the C3 enolpyruvate substate to UDP-methyl-N-acetylmuramic acid in the presence of NADPH. The overall product of this metabolic pathway, petidoglycan, is a biopolymer unique to Gram-positive and Gram-negative bacteria for which is essential for maintaining osmotic cell wall integrity. 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.
The ability of MurB to catalyse the stereo-selective reduction of both E and Z isomers of the substrate is thought to result from the active site architecture restricting free rotation around the C2-C3 bond, and slowing the rate relative to reprotonation. Structural data show the functional groups thought to be involved in the hydride transfer to C3 and protonation at C2 of the enol-ether substrate are arranged anti relative to the enol-double bond. From this information, the stereochemical outcome was predicted to yield a 2R,3R-dideuterio product. This product was later identified using chemical synthetic analysis and comparative NMR.
|AA||Uniprot||Uniprot Resid||PDB||PDB Resid|
overall reactant used, proton transfer, overall product formed, native state of cofactor regenerated, intermediate formation, native state of enzyme regenerated, native state of cofactor is not regenerated, inferred reaction step, cofactor used, intermediate collapse, hydride transfer
NADPH binds in close proximity to Ser229 and transfers a hydrogen to the N5 of the enzyme bound flavin cofactor. It is uncertain which residues are specifically involved in promoting the hydride transfer from the NADPH cofactor to the enzyme bound flavin. NMR analysis indicates NADPH to bind in the vicinity of Ser229, as well as several aromatic residues [PMID:9020777]. A monovalent cation is required for catalysis, although no metal is present in the crystal structure.
Glu325 acts as a general base, taking back the enol proton. This initiates the conjugate, stereo-selective proton abstraction by the enolate from Ser229. For MerB to catalyse the stereoselective reduction of both E and Z substrate isomers, the rate of rotation of the C2-C3 bond must be slow relative to reprotonation. The active site architecture ensures stereoselective discrimination in the formation of the enantio-selective product [PMID:8634262].
There are no kinetic parameters information for this Enzyme
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