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Molecular dynamics simulations reveal the conformational flexibility of Lipid II and its loose association with the defensin plectasin in the Staphylococcus aureus membrane

Molecular dynamics simulations reveal the conformational flexibility of Lipid II and its loose association with the defensin plectasin in the Staphylococcus aureus membrane
Molecular dynamics simulations reveal the conformational flexibility of Lipid II and its loose association with the defensin plectasin in the Staphylococcus aureus membrane
Lipid II is critical for peptidoglycan synthesis, which is the main component of the bacterial cell wall. Lipid II is a relatively conserved and important part of the cell wall biosynthesis pathway and is targeted by antibiotics such as the lantibiotics, which achieve their function by disrupting the biosynthesis of the cell wall. Given the urgent need for development of novel antibiotics to counter the growing threat of bacterial infection resistance, it is imperative that a thorough molecular-level characterization of the molecules targeted by antibiotics be achieved. To this end, we present a molecular dynamics simulation study of the conformational dynamics of Lipid II within a detailed model of the Staphylococcus aureus cell membrane. We show that Lipid II is able to adopt a range of conformations, even within the packed lipidic environment of the membrane. Our simulations also reveal dimerization of Lipid II mediated by cations. In the presence of the defensin peptide plectasin, the conformational lability of Lipid II allows it to form loose complexes with the protein, via a number of different binding modes.
3303-3314
Witzke, Sarah
0487f246-8b27-47a3-979c-e9f5c4a05f82
Petersen, Michael
30adb03e-dae7-4149-8fe5-d5a1aa33ec0a
Carpenter, Timothy S.
f46feb20-3a47-49e8-8d21-9f24b69c9d0a
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Witzke, Sarah
0487f246-8b27-47a3-979c-e9f5c4a05f82
Petersen, Michael
30adb03e-dae7-4149-8fe5-d5a1aa33ec0a
Carpenter, Timothy S.
f46feb20-3a47-49e8-8d21-9f24b69c9d0a
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394

Witzke, Sarah, Petersen, Michael, Carpenter, Timothy S. and Khalid, Syma (2016) Molecular dynamics simulations reveal the conformational flexibility of Lipid II and its loose association with the defensin plectasin in the Staphylococcus aureus membrane. Biochemistry, 55 (23), 3303-3314. (doi:10.1021/acs.biochem.5b01315).

Record type: Article

Abstract

Lipid II is critical for peptidoglycan synthesis, which is the main component of the bacterial cell wall. Lipid II is a relatively conserved and important part of the cell wall biosynthesis pathway and is targeted by antibiotics such as the lantibiotics, which achieve their function by disrupting the biosynthesis of the cell wall. Given the urgent need for development of novel antibiotics to counter the growing threat of bacterial infection resistance, it is imperative that a thorough molecular-level characterization of the molecules targeted by antibiotics be achieved. To this end, we present a molecular dynamics simulation study of the conformational dynamics of Lipid II within a detailed model of the Staphylococcus aureus cell membrane. We show that Lipid II is able to adopt a range of conformations, even within the packed lipidic environment of the membrane. Our simulations also reveal dimerization of Lipid II mediated by cations. In the presence of the defensin peptide plectasin, the conformational lability of Lipid II allows it to form loose complexes with the protein, via a number of different binding modes.

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Accepted/In Press date: 31 March 2016
e-pub ahead of print date: 9 May 2016
Published date: 14 June 2016
Organisations: Computational Systems Chemistry

Identifiers

Local EPrints ID: 399890
URI: http://eprints.soton.ac.uk/id/eprint/399890
PURE UUID: 63478399-f2de-46e2-9865-e64f0d299ed6
ORCID for Syma Khalid: ORCID iD orcid.org/0000-0002-3694-5044

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Date deposited: 05 Sep 2016 09:04
Last modified: 15 Mar 2024 05:51

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Contributors

Author: Sarah Witzke
Author: Michael Petersen
Author: Timothy S. Carpenter
Author: Syma Khalid ORCID iD

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