Homology modeling and docking studies of BjGL, a novel (+) gamma-lactamase from Bradyrhizobium japonicum.
(+) 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.
State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing, People's Republic of China.
Dawei
D
Song
State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing, People's Republic of China.
Shaozhou
S
Zhu
Beijing Institute of Pharmacology and Toxicology, Beijing, People's Republic of China.
Xingzhou
X
Li
State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing, People's Republic of China. Electronic address: zhenggj@mail.buct.edu.cn.
Guojun
G
Zheng
D000581:Amidohydrolases / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D020369:Bradyrhizobium / Q000737:chemistry* / Q000201:enzymology; D020134:Catalytic Domain; D006860:Hydrogen Bonding; D006868:Hydrolysis; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D016415:Sequence Alignment; D013379:Substrate Specificity
D008024:Ligands; D000581:Amidohydrolases; C401943:gamma-lactamase
(+) Gamma-lactamases; BjGL; Enantioselective hydrolysis; Homology modeling; Molecular docking