1T5M

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

Summary for 1T5M

• Entry DOI: 10.2210/pdb1t5m/pdb
• Related: 1T5N 1XT7
• NMR Information: BMRB: 6246
• 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

Jung, D.,Rozek, A.,Okon, M.,Hancock, R.E. (deposition date: 2004-05-04, release date: 2004-08-31, Last modification date: 2012-12-12)

Primary citation

Jung, D.,Rozek, A.,Okon, M.,Hancock, R.E.
Structural Transitions as Determinants of the Action of the Calcium-Dependent Antibiotic Daptomycin.
Chem.Biol., 11:949-, 2004

PubMed Abstract: 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.

PubMed: 15271353
DOI: 10.1016/J.CHEMBIOL.2004.04.020

Experimental method

SOLUTION NMR