1T5M

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

1T5M の概要

• エントリーDOI: 10.2210/pdb1t5m/pdb
• 関連するPDBエントリー: 1T5N 1XT7
• NMR情報: BMRB: 6246
• 関連するBIRD辞書のPRD_ID: PRD_000217
• 分子名称: DAPTOMYCIN, DECANOIC ACID (2 entities in total)
• 機能のキーワード: daptomycin, cubicin, antibiotic, lipopeptide, calcium-dependent
• 由来する生物種: STREPTOMYCES ROSEOSPORUS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1656.70

構造登録者

Jung, D.,Rozek, A.,Okon, M.,Hancock, R.E. (登録日: 2004-05-04, 公開日: 2004-08-31, 最終更新日: 2025-03-26)

主引用文献

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

実験手法

SOLUTION NMR