Direct and stereospecific interaction of amphidinol 3 with sterol in lipid bilayers

Rafael Atillo Espiritu, Nobuaki Matsumori, Masashi Tsuda, Michio Murata

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Amphidinol 3 (AM3), a polyhydroxy-polyene metabolite from the dinoflagellate Amphidinium klebsii, possesses potent antifungal activity. Although AM3 permeabilizes phospholipid membranes only in the presence of sterol, the detailed molecular basis by which AM3 recognizes sterols in membranes remains unknown. Here, we investigated the molecular interaction between sterols and AM3 in membranes from the viewpoint of stereospecific molecular recognition using ergosterol, cholesterol, and epicholesterol, which is the 3-OH epimer of cholesterol. Dye leakage assays, surface plasmon resonance experiments, 2H and 31P NMR measurements, and microscopic observations revealed that AM3 directly interacts with membrane sterols through the strict molecular recognition of the stereochemistry of the sterol 3-OH group. The direct interaction enhances the membrane binding efficiency of AM3, which subsequently permeabilizes membranes without altering membrane integrity.

Original languageEnglish
Pages (from-to)3287-3293
Number of pages7
JournalBiochemistry
Volume53
Issue number20
DOIs
Publication statusPublished - May 27 2014
Externally publishedYes

Fingerprint

Lipid bilayers
Lipid Bilayers
Sterols
Membranes
Molecular recognition
Cholesterol
Polyenes
Dinoflagellida
Ergosterol
Stereochemistry
Stereoisomerism
Surface Plasmon Resonance
Molecular interactions
Surface plasmon resonance
Metabolites
amphidinol 3
Assays
Phospholipids
Coloring Agents
Nuclear magnetic resonance

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Direct and stereospecific interaction of amphidinol 3 with sterol in lipid bilayers. / Espiritu, Rafael Atillo; Matsumori, Nobuaki; Tsuda, Masashi; Murata, Michio.

In: Biochemistry, Vol. 53, No. 20, 27.05.2014, p. 3287-3293.

Research output: Contribution to journalArticle

Espiritu, Rafael Atillo ; Matsumori, Nobuaki ; Tsuda, Masashi ; Murata, Michio. / Direct and stereospecific interaction of amphidinol 3 with sterol in lipid bilayers. In: Biochemistry. 2014 ; Vol. 53, No. 20. pp. 3287-3293.
@article{f9998db5e9934c2f9f64bb52eaf50c30,
title = "Direct and stereospecific interaction of amphidinol 3 with sterol in lipid bilayers",
abstract = "Amphidinol 3 (AM3), a polyhydroxy-polyene metabolite from the dinoflagellate Amphidinium klebsii, possesses potent antifungal activity. Although AM3 permeabilizes phospholipid membranes only in the presence of sterol, the detailed molecular basis by which AM3 recognizes sterols in membranes remains unknown. Here, we investigated the molecular interaction between sterols and AM3 in membranes from the viewpoint of stereospecific molecular recognition using ergosterol, cholesterol, and epicholesterol, which is the 3-OH epimer of cholesterol. Dye leakage assays, surface plasmon resonance experiments, 2H and 31P NMR measurements, and microscopic observations revealed that AM3 directly interacts with membrane sterols through the strict molecular recognition of the stereochemistry of the sterol 3-OH group. The direct interaction enhances the membrane binding efficiency of AM3, which subsequently permeabilizes membranes without altering membrane integrity.",
author = "Espiritu, {Rafael Atillo} and Nobuaki Matsumori and Masashi Tsuda and Michio Murata",
year = "2014",
month = "5",
day = "27",
doi = "10.1021/bi5002932",
language = "English",
volume = "53",
pages = "3287--3293",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "20",

}

TY - JOUR

T1 - Direct and stereospecific interaction of amphidinol 3 with sterol in lipid bilayers

AU - Espiritu, Rafael Atillo

AU - Matsumori, Nobuaki

AU - Tsuda, Masashi

AU - Murata, Michio

PY - 2014/5/27

Y1 - 2014/5/27

N2 - Amphidinol 3 (AM3), a polyhydroxy-polyene metabolite from the dinoflagellate Amphidinium klebsii, possesses potent antifungal activity. Although AM3 permeabilizes phospholipid membranes only in the presence of sterol, the detailed molecular basis by which AM3 recognizes sterols in membranes remains unknown. Here, we investigated the molecular interaction between sterols and AM3 in membranes from the viewpoint of stereospecific molecular recognition using ergosterol, cholesterol, and epicholesterol, which is the 3-OH epimer of cholesterol. Dye leakage assays, surface plasmon resonance experiments, 2H and 31P NMR measurements, and microscopic observations revealed that AM3 directly interacts with membrane sterols through the strict molecular recognition of the stereochemistry of the sterol 3-OH group. The direct interaction enhances the membrane binding efficiency of AM3, which subsequently permeabilizes membranes without altering membrane integrity.

AB - Amphidinol 3 (AM3), a polyhydroxy-polyene metabolite from the dinoflagellate Amphidinium klebsii, possesses potent antifungal activity. Although AM3 permeabilizes phospholipid membranes only in the presence of sterol, the detailed molecular basis by which AM3 recognizes sterols in membranes remains unknown. Here, we investigated the molecular interaction between sterols and AM3 in membranes from the viewpoint of stereospecific molecular recognition using ergosterol, cholesterol, and epicholesterol, which is the 3-OH epimer of cholesterol. Dye leakage assays, surface plasmon resonance experiments, 2H and 31P NMR measurements, and microscopic observations revealed that AM3 directly interacts with membrane sterols through the strict molecular recognition of the stereochemistry of the sterol 3-OH group. The direct interaction enhances the membrane binding efficiency of AM3, which subsequently permeabilizes membranes without altering membrane integrity.

UR - http://www.scopus.com/inward/record.url?scp=84901389268&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901389268&partnerID=8YFLogxK

U2 - 10.1021/bi5002932

DO - 10.1021/bi5002932

M3 - Article

C2 - 24773476

AN - SCOPUS:84901389268

VL - 53

SP - 3287

EP - 3293

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 20

ER -