PMID:13129913
| Citation |
Eschenburg, S, Kabsch, W, Healy, ML and Schonbrunn, E (2003) A new view of the mechanisms of UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) and 5-enolpyruvylshikimate-3-phosphate synthase (AroA) derived from X-ray structures of their tetrahedral reaction intermediate states. J. Biol. Chem. 278:49215-22 |
|---|---|
| Abstract |
UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) and 5-enolpyruvylshikimate-3-phosphate synthase (AroA) constitute the small enzyme family of enolpyruvyl transferases, which catalyze the chemically unusual reaction of enolpyruvyl transfer. MurA catalyzes the first step in the biosynthesis of the bacterial cell wall; AroA is the sixth enzyme of the shikimate pathway leading to the synthesis of aromatic compounds in numerous microorganisms and plants. Because both metabolic pathways are absent from mammals but essential for the growth of microorganisms, MurA and AroA are attractive targets for the development of novel antimicrobial drugs. We have determined the x-ray structures of the D305A mutant of Enterobacter cloacae MurA and the D313A mutant of Escherichia coli AroA, both of which crystallized in the presence of their substrates. The structures depict the tetrahedral reaction intermediate states of the enzymes and prove that, without the aspartate side chain, the overall addition-elimination reaction in both enzymes is halted after the addition step. The presented structures lead to a new view of the catalytic mechanism and, moreover, provide an ideal starting point for the rational design of potent inhibitors of MurA and AroA. |
| Links |
PubMed Online version:10.1074/jbc.M309741200 |
| Keywords |
3-Phosphoshikimate 1-Carboxyvinyltransferase; Alkyl and Aryl Transferases/chemistry; Alkyl and Aryl Transferases/metabolism; Crystallography, X-Ray; Enterobacter cloacae/enzymology; Models, Molecular |
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