Homology modeling and docking studies of BjGL, a novel (+) gamma-lactamase from Bradyrhizobium japonicum

• Homology model of a novel (+) gamma-lactamase was constructed and refined.
• The specific substrate (+) gamma-lactam was docked into the active site.
• The active site, binding pocket, and key residues of BjGL were identified.
• A potential mechanism of (+) gamma-lactam hydrolysis was proposed.

(+) Gamma-lactamases are enantioselective hydrolysis enzymes that can be used to produce optically pure (−) gamma-lactam, an important pharmaceutical intermediate for the anti-AIDS drug Abacavir. In this study, homology modeling and molecular dynamic simulation studies of a 3D homology model of BjGL, a novel (+) gamma-lactamase from Bradyrhizobium japonicum, were constructed and refined. The specific substrate (+) gamma-lactam and its enantiomer (−) gamma-lactam which can not be hydrolyzed was docked into the active site respectively, and the catalytic triad and other crucial residues that participate in the formation of the hydrophobic binding pocket, hydrogen bonds, and the oxyanion hole were identified. Furthermore, possible reasons for the high diastereoselectivity of BjGL binding with the substrate are proposed.

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