title: Spectroscopy analysis and molecular dynamics studies on the binding of penicillin V and sulbactam to beta-lactamase II from Bacillus cereus.
abstract: The molecular recognition and interaction of beta-lactamase II from Bacillus cereus (Bc II) with penicillin V (PV) and sulbactam (Sul) especially conformational changes of Bc II in the binding process were studied through spectroscopy analysis in combination with molecular dynamics (MD) simulation. The results show that in the binding process, a new coordination bond is observed between the Zn2of Bc II and the carboxyl-O of PV or Sul by replacing His204. Electrostatic interaction between Zn2and the ligand provide main driving force for the binding affinity. Compared with apo Bc II, there are mainly four loops showing significant conformational changes in ligand-bound Bc II. A weak conformational transformation from β-sheets to random coils is observed in the loop2 of ligand-bound Bc II. The conformational transformation may depend on the functional group and binding pose of the ligand, giving the binding pocket greater flexibility and accordingly allowing for an induced fit of the enzyme-ligand binding site around the newly introduced ligand. The change in the loop2 of ligand-bound Bc II may lead to the opening of the binding pocket of Bc II. Therefore, loop2 can be considered a gate for control of ligand access in Bc II, hence its dynamic response should be considered in new drug design and development.
authors.affiliation: College of Life Science, Northwest University, Xi'an 710069, China.
authors.forename: Penghui
authors.initials: P
authors.lastname: Shi
authors.affiliation: College of Life Science, Northwest University, Xi'an 710069, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Qiao
authors.affiliation: College of Life Science, Northwest University, Xi'an 710069, China.
authors.forename: Yeli
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Life Science, Northwest University, Xi'an 710069, China.
authors.forename: Shuaihua
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Life Science, Northwest University, Xi'an 710069, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Feng
authors.affiliation: College of Life Science, Northwest University, Xi'an 710069, China. Electronic address: bianliujiao@sohu.com.
authors.forename: Liujiao
authors.initials: L
authors.lastname: Bian
mesh_terms: D001409:Bacillus cereus / Q000378:metabolism*; D001665:Binding Sites / Q000502:physiology; D002510:Cephalosporinase / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D010404:Penicillin V / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D000072757:Protein Conformation, beta-Strand; D013057:Spectrum Analysis / Q000379:methods; D055672:Static Electricity; D013407:Sulbactam / Q000378:metabolism*
chemical_list: D002510:Cephalosporinase; D013407:Sulbactam; D010404:Penicillin V
keywords: Beta-lactamase II from Bacillus cereus; Molecular dynamics simulations; Penicillin V; Spectroscopy analysis; Sulbactam