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Spectroscopy analysis and molecular dynamics studies on the binding of penicillin V and sulbactam to beta-lactamase II from Bacillus cereus.
J Pharm Biomed Anal. 2017 May 10; 138:206-214.JP

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 Zn2 of Bc II and the carboxyl-O of PV or Sul by replacing His204. Electrostatic interaction between Zn2 and 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.

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Authors+Show Affiliations

College of Life Science, Northwest University, Xi'an 710069, China.

College of Life Science, Northwest University, Xi'an 710069, China.

College of Life Science, Northwest University, Xi'an 710069, China.

College of Life Science, Northwest University, Xi'an 710069, China.

College of Life Science, Northwest University, Xi'an 710069, China.

College of Life Science, Northwest University, Xi'an 710069, China. Electronic address: bianliujiao@sohu.com.

MeSH

Bacillus cereusBinding SitesCephalosporinaseMolecular Dynamics SimulationPenicillin VProtein BindingProtein Conformation, beta-StrandSpectrum AnalysisStatic ElectricitySulbactam

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28219797

Citation

Shi, Penghui, et al. "Spectroscopy Analysis and Molecular Dynamics Studies On the Binding of Penicillin V and Sulbactam to Beta-lactamase II From Bacillus Cereus." Journal of Pharmaceutical and Biomedical Analysis, vol. 138, 2017, pp. 206-214.

Shi P, Qiao P, Zhang Y, et al. Spectroscopy analysis and molecular dynamics studies on the binding of penicillin V and sulbactam to beta-lactamase II from Bacillus cereus. J Pharm Biomed Anal. 2017;138:206-214.

Shi, P., Qiao, P., Zhang, Y., Li, S., Feng, X., & Bian, L. (2017). Spectroscopy analysis and molecular dynamics studies on the binding of penicillin V and sulbactam to beta-lactamase II from Bacillus cereus. Journal of Pharmaceutical and Biomedical Analysis, 138, 206-214. https://doi.org/10.1016/j.jpba.2017.02.017

Shi P, et al. Spectroscopy Analysis and Molecular Dynamics Studies On the Binding of Penicillin V and Sulbactam to Beta-lactamase II From Bacillus Cereus. J Pharm Biomed Anal. 2017 May 10;138:206-214. PubMed PMID: 28219797.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Spectroscopy analysis and molecular dynamics studies on the binding of penicillin V and sulbactam to beta-lactamase II from Bacillus cereus. AU - Shi,Penghui, AU - Qiao,Pan, AU - Zhang,Yeli, AU - Li,Shuaihua, AU - Feng,Xuan, AU - Bian,Liujiao, Y1 - 2017/02/11/ PY - 2016/10/24/received PY - 2017/02/08/revised PY - 2017/02/09/accepted PY - 2017/2/22/pubmed PY - 2017/6/29/medline PY - 2017/2/22/entrez KW - Beta-lactamase II from Bacillus cereus KW - Molecular dynamics simulations KW - Penicillin V KW - Spectroscopy analysis KW - Sulbactam SP - 206 EP - 214 JF - Journal of pharmaceutical and biomedical analysis JO - J Pharm Biomed Anal VL - 138 N2 - 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 Zn2 of Bc II and the carboxyl-O of PV or Sul by replacing His204. Electrostatic interaction between Zn2 and 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. SN - 1873-264X UR - https://www.unboundmedicine.com/medline/citation/28219797/Spectroscopy_analysis_and_molecular_dynamics_studies_on_the_binding_of_penicillin_V_and_sulbactam_to_beta-lactamase_II_from_Bacillus_cereus. L2 - https://linkinghub.elsevier.com/retrieve/pii/S0731-7085(16)30934-7 DB - PRIME DP - Unbound Medicine ER -