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dc.contributor.authorTaylor, Robert
dc.contributor.authorButt, Khalida
dc.contributor.authorScott, Bradley
dc.contributor.authorZhang, TianHua
dc.contributor.authorMuraih, Jawad K.
dc.contributor.authorMintzer, Evan
dc.contributor.authorTaylor, Scott D.
dc.contributor.authorPalmer, Michael 17:14:19 (GMT) 17:14:19 (GMT)
dc.descriptionThe final publication is available at Elsevier via © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
dc.description.abstractDaptomycin and A54145 are homologous lipopeptide antibiotics that permeabilize the cell membranes of Gram-positive bacteria. Membrane permeabilization depends on the presence of both phosphatidylglycerol (PG) and calcium, and it involves the formation of oligomeric transmembrane pores that consist of approximately 6-8 subunits. We here show that each lipopeptide molecule binds two calcium ions in separable, successive steps. The first calcium ion causes the lipopeptide molecule to bind to the target membrane, and likely to form a loosely associated oligomer. Higher calcium concentrations induce binding of a second ion, which produces the more tightly associated and more deeply membrane-inserted final, functional form of the oligomer. Both calcium dependent steps are accompanied by fluorescence signals that indicate transition of specific amino acid residues into less polar environments, suggestive of insertion into the target membrane. Our findings agree with the earlier observation that two of the four acidic amino acid residues in the daptomycin molecule are essential for antibacterial activity. (C) 2016 Elsevier B.V. All rights reserved.en
dc.description.sponsorshipThis study was supported by operating grants by NSERC to Scott Taylor (155283-2012) and Michael Palmer (250265-2013).en
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.subjectLipid membranesen
dc.titleTwo successive calcium-dependent transitions mediate membrane binding and oligomerization of daptomycin and the related antibiotic A54145en
dcterms.bibliographicCitationTaylor, R., Butt, K., Scott, B., Zhang, T., Muraih, J. K., Mintzer, E., … Palmer, M. (2016). Two successive calcium-dependent transitions mediate membrane binding and oligomerization of daptomycin and the related antibiotic A54145. Biochimica Et Biophysica Acta-Biomembranes, 1858(9), 1999–2005.
uws.contributor.affiliation1Faculty of Scienceen

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