Molecular dynamics simulation of the complex PBP-2x with drug cefuroxime to explore the drug resistance mechanism of Streptococcus suis R61.

PloS One
Yan GeJun Yu

Abstract

Drug resistance of Streptococcus suis strains is a worldwide problem for both humans and pigs. Previous studies have noted that penicillin-binding protein (PBPs) mutation is one important cause of β-lactam antibiotic resistance. In this study, we used the molecular dynamics (MD) method to study the interaction differences between cefuroxime (CES) and PBP2x within two newly sequenced Streptococcus suis: drug-sensitive strain A7, and drug-resistant strain R61. The MM-PBSA results proved that the drug bound much more tightly to PBP2x in A7 (PBP2x-A7) than to PBP2x in R61 (PBP2x-R61). This is consistent with the evidently different resistances of the two strains to cefuroxime. Hydrogen bond analysis indicated that PBP2x-A7 preferred to bind to cefuroxime rather than to PBP2x-R61. Three stable hydrogen bonds were formed by the drug and PBP2x-A7, while only one unstable bond existed between the drug and PBP2x-R61. Further, we found that the Gln569, Tyr594, and Gly596 residues were the key mutant residues contributing directly to the different binding by pair wise energy decomposition comparison. By investigating the binding mode of the drug, we found that mutant residues Ala320, Gln553, and Thr595 indirectly affected the final phenom...Continue Reading

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Citations

May 21, 2013·Animal Health Research Reviews·Norma P VarelaJeff Wilson
Nov 8, 2015·Journal of Molecular Graphics & Modelling·Arunkumar VenkatesanSujatha Narayanan
Aug 8, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Vertika GautamVannajan Sanghiran Lee

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Modeller
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GBTOT
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molsurf
Xleap
Delphi
Amber
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Genedoc

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