Ion channel complex of antibiotics as viewed by NMR

Michio Murata, Yusuke Kasai, Yuichi Umegawa, Naohiro Matsushita, Hiroshi Tsuchikawa, Nobuaki Matsumori, Tohru Oishi

研究成果: Contribution to journalArticle査読

13 被引用数 (Scopus)

抄録

Amphotericin B (AmB) exerts its pharmacological effects by forming a barrel-stave assembly in fungal membranes. To examine the interaction between AmB and ergosterol or cholesterol, 13C- and 19F-labeled covalent conjugates were prepared and subjected to solidstate NMR measurements. Using rotor-synchronous double-resonance experiments such as rotational echo double resonance (REDOR) and RDX, we estimated the distance between the fluorine atom and its nearest carbon in the heptaene moiety to be less than 8.6 A ̊, indicating that the B ring of ergosterol comes close to the AmB polyene moiety. Conformational search of the AmB-ergosterol conjugate using the NMR-derived constraints suggested that ergosterol molecules surround the AmB assembly in contrast to the conventional image where ergosterol is inserted into AmB molecules. AmB-AmB bimolecular interaction was examined by using 13C- and 19F-labeled AmBs in dimyritoylphosphatidylcholine (DMPC) membrane without sterols. 13C- and 19F dipolar interactions deriving from both head-to-head and head-to-tail orientations were observed in the REDOR experiments. The interactions between AmB and acyl chains of the phospholipid were also detected.

本文言語英語
ページ(範囲)1123-1129
ページ数7
ジャーナルPure and Applied Chemistry
81
6
DOI
出版ステータス出版済み - 7 24 2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)

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