title: Insight into the effect of inhibitor resistant S130G mutant on physico-chemical properties of SHV type beta-lactamase: a molecular dynamics study.
abstract: Bacterial resistance is a serious threat to human health. The production of β-lactamase, which inactivates β-lactams is most common cause of resistance to the β-lactam antibiotics. The Class A enzymes are most frequently encountered among the four β-lactamases in the clinic isolates. Mutations in class A β-lactamases play a crucial role in substrate and inhibitor specificity. SHV and TEM type are known to be most common class A β-lactamases. In the present study, we have analyzed the effect of inhibitor resistant S130G point mutation of SHV type Class-A β-lactamase using molecular dynamics and other in silico approaches. Our study involved the use of different in silico methods to investigate the affect of S130G point mutation on the major physico-chemical properties of SHV type class A β-lactamase. We have used molecular dynamics approach to compare the dynamic behaviour of native and S130G mutant form of SHV β-lactamase by analyzing different properties like root mean square deviation (RMSD), H-bond, Radius of gyration (Rg) and RMS fluctuation of mutation. The results clearly suggest notable loss in the stability of S130G mutant that may further lead to decrease in substrate specificity of SHV. Molecular docking further indicates that S130G mutation decreases the binding affinity of all the three inhibitors in clinical practice.
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India; Department of Biosciences, Integral University, Lucknow, India.
authors.forename: Mohd Hassan
authors.initials: MH
authors.lastname: Baig
authors.affiliation: School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, India.
authors.forename: D Raja
authors.initials: DR
authors.lastname: Sudhakar
authors.affiliation: National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Ponnusamy
authors.initials: P
authors.lastname: Kalaiarasan
authors.affiliation: School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Naidu
authors.initials: N
authors.lastname: Subbarao
authors.affiliation: Department of Biotechnology, Government of India, New Delhi, India.
authors.forename: Gulshan
authors.initials: G
authors.lastname: Wadhawa
authors.affiliation: Department of Biosciences, Integral University, Lucknow, India.
authors.forename: Mohtashim
authors.initials: M
authors.lastname: Lohani
authors.affiliation: Department of Biosciences, Integral University, Lucknow, India.
authors.forename: M Kalim A
authors.initials: MK
authors.lastname: Khan
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
authors.forename: Asad U
authors.initials: AU
authors.lastname: Khan
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000627:therapeutic use; D004352:Drug Resistance, Microbial / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D017354:Point Mutation; D011487:Protein Conformation; D065093:beta-Lactamase Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D001618:beta-Lactamases / Q000737:chemistry* / Q000235:genetics; D047090:beta-Lactams / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D001618:beta-Lactamases