1mbt
From Proteopedia
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OXIDOREDUCTASE
Overview
BACKGROUND: The repeating disaccharide and pentapeptide units of the bacterial peptidoglycan layer are connected by a lactyl ether bridge biosynthesized from UDP-N-acetylglucosamine and phosphoenolpyruvate in sequential enol ether transfer and reduction steps catalyzed by MurA and MurB respectively. Knowledge of the structure and mechanism of the MurB enzyme will permit analysis of this unusual enol ether reduction reaction and may facilitate the design of inhibitors as candidate next-generation antimicrobial agents. RESULTS: The crystal structure of UDP-N-acetylenolpyruvylglucosamine reductase, MurB, has been solved at 3.0 A and compared with our previously reported structure of MurB complexed with its substrate enolpyruvyl-UDP-N- acetylglucosamine. Comparison of the liganded structure of MurB with this unliganded form reveals that the binding of substrate induces a substantial movement of domain 3 (residues 219-319) of the enzyme and a significant rearrangement of a loop within this domain. These ligand induced changes disrupt a stacking interaction between two tyrosines (Tyr190 and Tyr254) which lie at the side of the channel leading to the active site of the free enzyme. CONCLUSIONS: The conformational change induced by enolpyruvyl-UDP-N- acetylglucosamine binding to MurB results in the closure of the substrate-binding channel over the substrate. Tyr190 swings over the channel opening and establishes a hydrogen bond with an oxygen of the alpha-phosphate of the sugar nucleotide substrate which is critical to substrate binding.
About this Structure
1MBT is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as UDP-N-acetylmuramate dehydrogenase, with EC number 1.1.1.158 Full crystallographic information is available from OCA.
Reference
The structure of the substrate-free form of MurB, an essential enzyme for the synthesis of bacterial cell walls., Benson TE, Walsh CT, Hogle JM, Structure. 1996 Jan 15;4(1):47-54. PMID:8805513
Page seeded by OCA on Thu Feb 21 13:53:37 2008
