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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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Related in: MedlinePlus

Potential energy (kJ/mol) of native and mutant type SHV β-lactamases.Native is shown in black; S130G mutant form of SHV β-lactamases is shown in red.
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pone-0112456-g005: Potential energy (kJ/mol) of native and mutant type SHV β-lactamases.Native is shown in black; S130G mutant form of SHV β-lactamases is shown in red.

Mentions: The potential energy analyzed during the 10 ns molecular dynamics simulations for wild type and the mutant are shown in figure 5. The potential energy plot shows that all the molecular systems stabilized and remained stable throughout 10 ns of molecular dynamics simulations. The average of potential energy for each MD simulation shows that the potential energy during MDs with the wild type stabilized at approximately −806049.3047 kcal/mol, while the potential energy of mutant was found to be stabilized at approximately −754239.1479 kcal/mol.


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)

Potential energy (kJ/mol) of native and mutant type SHV β-lactamases.Native is shown in black; S130G mutant form of SHV β-lactamases is shown in red.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0112456-g005: Potential energy (kJ/mol) of native and mutant type SHV β-lactamases.Native is shown in black; S130G mutant form of SHV β-lactamases is shown in red.
Mentions: The potential energy analyzed during the 10 ns molecular dynamics simulations for wild type and the mutant are shown in figure 5. The potential energy plot shows that all the molecular systems stabilized and remained stable throughout 10 ns of molecular dynamics simulations. The average of potential energy for each MD simulation shows that the potential energy during MDs with the wild type stabilized at approximately −806049.3047 kcal/mol, while the potential energy of mutant was found to be stabilized at approximately −754239.1479 kcal/mol.

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