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NMR structure determination and calcium binding effects of lipopeptide antibiotic daptomycin.

L.-J. Ball, C.M. Goult, J.A. Donarski, J. Micklefield and V. Ramesh*

Org. Biomol. Chem. 2004;2:1872-1878.

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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 addn. to this, we have detd. 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. [on SciFinder (R)]

Bibliographic metadata

Type of resource:
Content type:
Published date:
Journal title:
ISSN:
Volume:
2
Start page:
1872
End page:
1878
Pagination:
1872-1878
Digital Object Identifier:
10.1039/b402722a
Related website(s):
  • Related website
Access state:
Active

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:1a4485
Created:
6th August, 2009, 14:11:15
Last modified:
17th November, 2012, 13:23:19

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