Structural Transitions as Determinants of the Action of the Calcium-Dependent Antibiotic Daptomycin
作者： David Jung , Annett Rozek , Mark Okon , Robert E.W Hancock
DOI: 10.1016/J.CHEMBIOL.2004.04.020
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摘要: Daptomycin is a cyclic anionic lipopeptide antibiotic recently approved for the treatment of complicated skin infections (Cubicin). Its function dependent on calcium (as Ca2+). Circular dichroism spectroscopy indicated that daptomycin experienced two structural transitions: transition upon interaction with Ca2+, and further Ca2+ bacterial acidic phospholipid, phosphatidyl glycerol. The Ca2+-dependent insertion into model membranes promoted mild more pronounced perturbations as assessed by increase lipid flip-flop membrane leakage, respectively. NMR structure induced conformational change in increased its amphipathicity. These results are consistent hypothesis association permits it to interact effects similar those cationic antimicrobial peptides.
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