Sandbox 130

New Delhi Metallo-β-Lactamase

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The New Delhi metallo-β-lactamase (NMD-1) in complex with meropenem (Chain A) demonstrates the mechanism in which the active site binds and hydrolyzed the a 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 and acts to suppress the pKa of the hyrdolytic water to (~5-6) to facilitate it's nucleophilic role. The active site contains key features for hydrolyzing carbapenems:

 Zinc ion 1(Zn1) is coordinated by three histidine residues:

H120, H122 and H189.

 Zinc ion 2 (Zn2) is coordinated by three residues: 250, C208, and D124.