Protonation state of Asp120 in the binuclear active site of the metallo-beta-lactamase from Bacteroides fragilis

The determination of the protonation state of enzyme active sites may be crucial for the investigation of their mechanism of action. In the bizinc beta-lactamase family of enzymes, no consensus has been reached on the protonation state of a fully conserved amino acid present in the active site, Asp120. To address this issue, we carry out here density functional theory (DFT) calculations on large models (based on Bacteroides fragilis X-ray structure) which include the metal coordination polyhedron and groups interacting with it. Our calculations suggest that Asp120 is ionized. The relevance of this finding for site-directed mutagenesis experiments on the 120 position and on the mechanism of action is discussed.

Published in:
Inorg Chem, 42, 14, 4245-7
International School for Advanced Studies, SISSA and INFM-DEmocritos MOdeling Center for Research in aTOmistic Simulation, via Beirut 2-4, 34014 Trieste, Italy.

 Record created 2008-04-28, last modified 2018-03-17

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