Vancomycin: ligand recognition, dimerization and super-complex formation

Jia, ZhiGuang, O'Mara, Megan L., Zuegg, Johannes, Cooper, Matthew A. and Mark, Alan E. (2013) Vancomycin: ligand recognition, dimerization and super-complex formation. FEBS Journal, 280 5: 1294-1307. doi:10.1111/febs.12121


Author Jia, ZhiGuang
O'Mara, Megan L.
Zuegg, Johannes
Cooper, Matthew A.
Mark, Alan E.
Title Vancomycin: ligand recognition, dimerization and super-complex formation
Journal name FEBS Journal   Check publisher's open access policy
ISSN 1742-464X
1742-4658
Publication date 2013-03
Year available 2013
Sub-type Article (original research)
DOI 10.1111/febs.12121
Open Access Status DOI
Volume 280
Issue 5
Start page 1294
End page 1307
Total pages 14
Place of publication West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Collection year 2014
Language eng
Formatted abstract
The antibiotic vancomycin targets lipid II, blocking cell wall synthesis in Gram-positive bacteria. Despite extensive study, questions remain regarding how it recognizes its primary ligand and what is the most biologically relevant form of vancomycin. In this study, molecular dynamics simulation techniques have been used to examine the process of ligand binding and dimerization of vancomycin. Starting from one or more vancomycin monomers in solution, together with different peptide ligands derived from lipid II, the simulations predict the structures of the ligated monomeric and dimeric complexes to within 0.1 nm rmsd of the structures determined experimentally. The simulations reproduce the conformation transitions observed by NMR and suggest that proposed differences between the crystal structure and the solution structure are an artifact of the way the NMR data has been interpreted in terms of a structural model. The spontaneous formation of both back-to-back and face-to-face dimers was observed in the simulations. This has allowed a detailed analysis of the origin of the cooperatively between ligand binding and dimerization and suggests that the formation of face-to-face dimers could be functionally significant. The work also highlights the possible role of structural water in stabilizing the vancomycin ligand complex and its role in the manifestation of vancomycin resistance. Molecular dynamics simulations have been used to examine the process of ligand binding and dimerization of vancomycin. The spontaneous formation of vancomycin-ligand complexes, back-to-back and face-to-face dimers was observed. This has allowed a detailed analysis of the origin of the cooperatively between ligand binding and dimerization and suggests that the formation of face-to-face dimers could be functionally significant
Keyword Antibiotic resistance
Computer simulation
Glycopeptide antibiotics
Lipid
Molecular dynamics
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes epub ahead of print

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
 
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Created: Fri, 11 Jan 2013, 14:45:01 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences