期刊
ACS OMEGA
卷 4, 期 20, 页码 18889-18899出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsomega.9b02949
关键词
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资金
- Danish Council for Independent Research | Technology and Production Sciences [FTP-0602-01778B]
- Danish National Research Foundation [DNRF59]
- Danish Centre for Scientific Computing (CSCAA)
- Alfred Benzon Fellowship
- Marie Curie Intra European Fellowship within the 7th European Community Framework Program
- Wellcome Trust
- BBSRC
- EPSRC
- Leverhulme Trust
- BBSRC [BB/R00126X/1] Funding Source: UKRI
- EPSRC [EP/R029407/1] Funding Source: UKRI
Cinnamycin is a lantibiotic peptide, which selectively binds to and permeabilizes membranes containing phosphatidylethanolamine (PE) lipids. As PE is a major component of many bacterial cell membranes, cinnamycin has considerable potential for destroying these. In this study, molecular dynamics simulations are used to elucidate the structure of a lipid-cinnamycin complex and the origin of selective lipid binding. The simulations reveal that cinnamycin selectively binds to PE by forming an extensive hydrogen-bonding network involving all three hydrogen atoms of the primary ammonium group of the PE head group. The substitution of a single hydrogen atom with a methyl group on the ammonium nitrogen destabilizes this hydrogen-bonding network. In addition to binding the primary ammonium group, cinnamycin also interacts with the phosphate group of the lipid through a previously uncharacterized phosphate-binding site formed by the backbone Phe10-Abu11-Phe12-Val13 moieties (Abu = 1-alpha-aminobutyric acid). In addition, hydroxylation of Asp15 at C beta plays a role in selective binding of PE due to its tight interaction with the charged amine of the lipid head group. The simulations reveal that the position and orientation of the peptide in the membrane depend on the type of lipid to which it binds, suggesting a reason for why cinnamycin selectively permeabilizes PE-containing membranes.
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