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Title: Molecular Dynamics Simulations Reveal the Conformational Flexibility of Lipid II and Its Loose Association with the Defensin Plectasin in the Staphylococcus aureus Membrane

Journal Article · · Biochemistry
 [1];  [2];  [3];  [4]
  1. Univ. of Southern Denmark, Odense (Denmark). Dept. of Physics, Chemistry and Pharmacy; Univ. of Southampton (United Kingdom). School of Chemistry
  2. Univ. of Southern Denmark, Odense (Denmark). Dept. of Physics, Chemistry and Pharmacy
  3. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division
  4. Univ. of Southampton (United Kingdom). School of Chemistry
+ Show Author Affiliations

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 here 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.

Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC52-07NA27344
OSTI ID:
1524722
Report Number(s):
LLNL-JRNL-679940; 802879
Journal Information:
Biochemistry, Vol. 55, Issue 23; ISSN 0006-2960
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 13 works
Citation information provided by
Web of Science

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Cited By (2)

Flotillin mediated membrane fluidity controls peptidoglycan synthesis and MreB movement posted_content April 2019
The role of the jaw subdomain of peptidoglycan glycosyltransferases for lipid II polymerization journal June 2018

Figures / Tables (15)

Figure 1(p. 9)figure Figure 1
Table 1(p. 10)table Table 1
Table 2(p. 11)table Table 2
Figure 2(p. 15)figure Figure 2
Figure 3(p. 16)figure Figure 3
Figure 4(p. 17)figure Figure 4
Figure 5(p. 18)figure Figure 5
Figure 6(p. 19)figure Figure 6
Figure 7(p. 21)figure Figure 7
Table 3(p. 22)table Table 3
Figure 8(p. 23)figure Figure 8
Figure 9(p. 24)figure Figure 9
Figure 10(p. 25)figure Figure 10
Figure 11(p. 26)figure Figure 11
Figure 12(p. 27)figure Figure 12

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