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Structural transitions as determinants of the action of the calcium-dependent antibiotic daptomycin

Overview

Daptomycin is a cyclic anionic lipopeptide antibiotic recently approved, for the treatment of complicated skin infections (Cubicin). Its function, is dependent on calcium (as Ca2+). Circular dichroism spectroscopy, indicated that daptomycin experienced two structural transitions: a, transition upon interaction of daptomycin with Ca2+, and a further, transition upon interaction with Ca2+ and the bacterial acidic, phospholipid, phosphatidyl glycerol. The Ca2+-dependent insertion of, daptomycin into model membranes promoted mild and more pronounced, perturbations as assessed by the increase of lipid flip-flop and membrane, leakage, respectively. The NMR structure of daptomycin indicated that Ca2+, induced a conformational change in daptomycin that increased its, amphipathicity. These results are consistent with the hypothesis that the, association of Ca2+ with daptomycin permits it to interact with bacterial, membranes with effects that are similar to those of the cationic, antimicrobial peptides.

About this Structure

1T5M is a Protein complex structure of sequences from [1] with DKA as ligand. Full crystallographic information is available from OCA.

Reference

Structural transitions as determinants of the action of the calcium-dependent antibiotic daptomycin., Jung D, Rozek A, Okon M, Hancock RE, Chem Biol. 2004 Jul;11(7):949-57. PMID:15271353

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