1XT7

Daptomycin NMR Structure

Summary for 1XT7

• Entry DOI: 10.2210/pdb1xt7/pdb
• Related: 1T5M 1T5N
• NMR Information: BMRB: 6420
• Related PRD ID: PRD_000217
• Descriptor: DAPTOMYCIN, DECANOIC ACID (2 entities in total)
• Functional Keywords: daptomycin, cubicin, antibiotic, lipopeptide, calcium-dependent
• Biological source: STREPTOMYCES ROSEOSPORUS
• Total number of polymer chains: 1
• Total formula weight: 1656.70

Authors

Ball, L.-J.,Goult, C.M.,Donarski, J.A.,Micklefield, J.,Ramesh, V. (deposition date: 2004-10-21, release date: 2004-11-16, Last modification date: 2025-03-26)

Primary citation

Ball, L.-J.,Goult, C.M.,Donarski, J.A.,Micklefield, J.,Ramesh, V.
NMR Structure Determination and Calcium Binding Effects of Lipopeptide Antibiotic Daptomycin
Org.Biomol.Chem., 2:1872-, 2004

PubMed 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.

PubMed: 15227539
DOI: 10.1039/B402722A

Experimental method

SOLUTION NMR