Sandbox 122
New Delhi Metallo-Beta-LactamaseNew Delhi Metallo-Beta-Lactamase
The New Delhi metallo-beta-lactamse in complex with meropenem demonstrates the mechanism in which the active site binds and hydrolyzes the carbapenem, in this case meropenem. Zn1, coordinated by three histidine residues, acts as a major constituent of oxyanion hole to stabilize tetrahedral intermediate. It also acts as a Lewis acid for interaction with lactam carbonyl in Michaelis complex. Zn1 also acts to suppress the pka of the hydrolytic water to (~5-6) to facilitate it's nucleophillic role.
|