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

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...

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Autores principales:	Yan Ge, Jiayan Wu, Yingjie Xia, Ming Yang, Jingfa Xiao, Jun Yu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dca3eabb2faa4e829c7b5e935dd68919
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spelling	oai:doaj.org-article:dca3eabb2faa4e829c7b5e935dd689192021-11-18T07:20:42ZMolecular dynamics simulation of the complex PBP-2x with drug cefuroxime to explore the drug resistance mechanism of Streptococcus suis R61.1932-620310.1371/journal.pone.0035941https://doaj.org/article/dca3eabb2faa4e829c7b5e935dd689192012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22563422/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Drug 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 phenomenon by topological conformation alteration. Above all, our results revealed some details about the specific interaction between the two PBP2x proteins and the drug cefuroxime. To some degree, this explained the drug resistance mechanism of Streptococcus suis and as a result could be helpful for further drug design or improvement.Yan GeJiayan WuYingjie XiaMing YangJingfa XiaoJun YuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35941 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yan Ge Jiayan Wu Yingjie Xia Ming Yang Jingfa Xiao Jun Yu Molecular dynamics simulation of the complex PBP-2x with drug cefuroxime to explore the drug resistance mechanism of Streptococcus suis R61.
description	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 phenomenon by topological conformation alteration. Above all, our results revealed some details about the specific interaction between the two PBP2x proteins and the drug cefuroxime. To some degree, this explained the drug resistance mechanism of Streptococcus suis and as a result could be helpful for further drug design or improvement.
format	article
author	Yan Ge Jiayan Wu Yingjie Xia Ming Yang Jingfa Xiao Jun Yu
author_facet	Yan Ge Jiayan Wu Yingjie Xia Ming Yang Jingfa Xiao Jun Yu
author_sort	Yan Ge
title	Molecular dynamics simulation of the complex PBP-2x with drug cefuroxime to explore the drug resistance mechanism of Streptococcus suis R61.
title_short	Molecular dynamics simulation of the complex PBP-2x with drug cefuroxime to explore the drug resistance mechanism of Streptococcus suis R61.
title_full	Molecular dynamics simulation of the complex PBP-2x with drug cefuroxime to explore the drug resistance mechanism of Streptococcus suis R61.
title_fullStr	Molecular dynamics simulation of the complex PBP-2x with drug cefuroxime to explore the drug resistance mechanism of Streptococcus suis R61.
title_full_unstemmed	Molecular dynamics simulation of the complex PBP-2x with drug cefuroxime to explore the drug resistance mechanism of Streptococcus suis R61.
title_sort	molecular dynamics simulation of the complex pbp-2x with drug cefuroxime to explore the drug resistance mechanism of streptococcus suis r61.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/dca3eabb2faa4e829c7b5e935dd68919
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Molecular dynamics simulation of the complex PBP-2x with drug cefuroxime to explore the drug resistance mechanism of Streptococcus suis R61.

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