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Insight into the effect of inhibitor resistant S130G mutant on physico-chemical properties of SHV type beta-lactamase: a molecular dynamics study.

Baig MH, Sudhakar DR, Kalaiarasan P, Subbarao N, Wadhawa G, Lohani M, Khan MK, Khan AU - PLoS ONE (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India; Department of Biosciences, Integral University, Lucknow, India.

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.

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Physico-chemical features of native and S130G mutant SHV studied.
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pone-0112456-g001: Physico-chemical features of native and S130G mutant SHV studied.

Mentions: To examine the effect of point mutation on the change in protein stability, the difference in folding free energy (ΔΔG) was calculated by the CUPSAT [26], I-mutant-2, Mustrad and PoPMuSiC-2.0 program [27]. Pymol was used for the visual analysis of the enzymes. Ligplot [28] was used to analyze the interaction within the complex. (Fig 1)


Insight into the effect of inhibitor resistant S130G mutant on physico-chemical properties of SHV type beta-lactamase: a molecular dynamics study.

Baig MH, Sudhakar DR, Kalaiarasan P, Subbarao N, Wadhawa G, Lohani M, Khan MK, Khan AU - PLoS ONE (2014)

Physico-chemical features of native and S130G mutant SHV studied.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4257546&req=5

pone-0112456-g001: Physico-chemical features of native and S130G mutant SHV studied.
Mentions: To examine the effect of point mutation on the change in protein stability, the difference in folding free energy (ΔΔG) was calculated by the CUPSAT [26], I-mutant-2, Mustrad and PoPMuSiC-2.0 program [27]. Pymol was used for the visual analysis of the enzymes. Ligplot [28] was used to analyze the interaction within the complex. (Fig 1)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India; Department of Biosciences, Integral University, Lucknow, India.

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.

Show MeSH
Related in: MedlinePlus