1t5m
From Proteopedia
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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]. 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
Page seeded by OCA on Thu Mar 20 14:14:06 2008
Categories: Protein complex | Hancock, R E. | Jung, D. | Okon, M. | Rozek, A. | DKA | Antibiotic | Calcium-dependent | Cubicin | Cyclic lipopeptide | Daptomycin | Drug
