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Issue 13, 2004
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NMR structure determination and calcium binding effects of lipopeptide antibiotic daptomycin

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Abstract

Daptomycin is an acidic lipopeptide antibiotic, whose three-dimensional structure and mechanism of action is currently unknown. Recently daptomycin, trade name Cubicin, was approved as a drug for the treatment of skin-related infections (M. Larkin Lancet, 2003, 3, 677) and became the first antibiotic of its class to be used in the clinic (A. Raja et al., Nature Rev. Drug Discov., 2003, 2, 943–944). We have carried out a systematic high field NMR study of daptomycin and its binding to calcium ions which is essential for antibiotic activity. In this first report, we demonstrate the sequence-specific resonance assignment of daptomycin under resolved NMR measurement conditions. In addition to this, we have determined the 3D structure of apo-daptomycin and demonstrated a 1 : 1 stoichiometry on the binding to calcium ions. We have also demonstrated that the binding of calcium ions does not result in major conformational changes, but does induce aggregation. This may be an important factor in the mode of action of daptomycin.

Graphical abstract: NMR structure determination and calcium binding effects of lipopeptide antibiotic daptomycin

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Publication details

The article was received on 23 Feb 2004, accepted on 10 May 2004 and first published on 15 Jun 2004


Article type: Paper
DOI: 10.1039/B402722A
Citation: Org. Biomol. Chem., 2004,2, 1872-1878
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    NMR structure determination and calcium binding effects of lipopeptide antibiotic daptomycin

    L. Ball, C. M. Goult, J. A. Donarski, J. Micklefield and V. Ramesh, Org. Biomol. Chem., 2004, 2, 1872
    DOI: 10.1039/B402722A

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