Conformation and location of membrane-bound salinomycin-sodium complex deduced from NMR in isotropic bicelles

Nobuaki Matsumori, Atsushi Morooka, Michio Murata

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

An ionophore antibiotic salinomycin was studied in a membrane environment consisting of isotropic bicelles, a better model for biological membranes than micelles, and its conformation and topological orientation in bicelles was determined. 2D NMR measurements and restrained conformational search revealed that salinomycin-sodium salt in bicelles adopts an open conformation in which the orientation of the E-ring is significantly different from that in crystal and solution structures. This conformational alteration breaks an intramolecular hydrogen bond between 28-OH and 1-O, dislocates the ether oxygen of the E-ring from a coordinated position to the sodium ion observed in the crystal, and consequently weakens the complexation between salinomycin and the sodium ion. Paramagnetic relaxation experiments using doxylphospholipids reveal that salinomycin is embedded shallowly in bicelles, with both terminals being closer to the water interface and the olefin portion facing the bicelle interior. Measurements of intermolecular NOEs between salinomycin and phospholipids further supported this orientation. Weaker complexation with sodium ion and positional preference in the membrane polar region may facilitate the catch-and-release of metal ions at the polar/nonpolar interface of bilayers. On the basis of these findings, a model for salinomycin-assisted transport of metal ions across biological membranes is proposed.

Original languageEnglish
Pages (from-to)14989-14995
Number of pages7
JournalJournal of the American Chemical Society
Volume129
Issue number48
DOIs
Publication statusPublished - Dec 5 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint Dive into the research topics of 'Conformation and location of membrane-bound salinomycin-sodium complex deduced from NMR in isotropic bicelles'. Together they form a unique fingerprint.

Cite this