title: Why tazobactam and sulbactam have different intermediates population with SHV-1 β-lactamase: a molecular dynamics study.
abstract: The imine intermediates of tazobactam and sulbactam bound to SHV-1 β-lactamase were investigated by molecular dynamics (MD) simulation respectively. Hydrogen bond networks around active site were found different between tazobactam and sulbactam acyl-enzymes. In tazobactam imine intermediate, it was observed that the triazolyl ring formed stable hydrogen bonds with Asn170 and Thr167. The results suggest that conformation of imine determined the population of intermediates. In imine intermediate of tazobactam, the triazolyl ring is trapped in Thr_Asn pocket, and it restricts the rotation of C5-C6 bond so that tazobactam can only generate trans enamine intermediate. Further, conformational cluster analyses are performed to substantiate the results. These findings provide an explanation for the corresponding experimental results, and will be potentially useful in the development of new inhibitors.
authors: Department of Chemistry, Liaocheng University, Liaocheng, 252059 Shandong, China.
authors: Rui
authors: R
authors: Li
authors: Yeng-Tseng
authors: YT
authors: Wang
authors: Cheng-Lung
authors: CL
authors: Chen
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013407:Sulbactam / Q000737:chemistry* / Q000378:metabolism; D000078142:Tazobactam; D001618:beta-Lactamases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D010397:Penicillanic Acid; C054882:beta-lactamase PIT-2; D001618:beta-Lactamases; D013407:Sulbactam; D000078142:Tazobactam