4M6E

The high resolution structure of tyrocidine A reveals an amphipathic dimer

4M6E の概要

• エントリーDOI: 10.2210/pdb4m6e/pdb
• 関連するBIRD辞書のPRD_ID: PRD_001142
• 分子名称: tyrocidine A, (4S)-2-METHYL-2,4-PENTANEDIOL, METHANOL, ... (4 entities in total)
• 機能のキーワード: cyclic peptide, antibiotic
• 由来する生物種: Bacillus brevis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1502.79

構造登録者

Loll, P.J.,Economou, N.J.,Nahoum, V. (登録日: 2013-08-09, 公開日: 2014-03-19, 最終更新日: 2025-03-26)

主引用文献

Loll, P.J.,Upton, E.C.,Nahoum, V.,Economou, N.J.,Cocklin, S.
The high resolution structure of tyrocidine A reveals an amphipathic dimer.
Biochim.Biophys.Acta, 1838:1199-1207, 2014

PubMed Abstract: Tyrocidine A, one of the first antibiotics ever to be discovered, is a cyclic decapeptide that binds to membranes of target bacteria, disrupting their integrity. It is active against a broad spectrum of Gram-positive organisms, and has recently engendered interest as a potential scaffold for the development of new drugs to combat antibiotic-resistant pathogens. We present here the X-ray crystal structure of tyrocidine A at a resolution of 0.95Å. The structure reveals that tyrocidine forms an intimate and highly amphipathic homodimer made up of four beta strands that associate into a single, highly curved antiparallel beta sheet. We used surface plasmon resonance and potassium efflux assays to demonstrate that tyrocidine binds tightly to mimetics of bacterial membranes with an apparent dissociation constant (K(D)) of 10 μM, and efficiently permeabilizes bacterial cells at concentrations equal to and below the K(D). Using variant forms of tyrocidine in which the fluorescent probe p-cyano-phenylalanine had been inserted on either the polar or apolar face of the molecule, we performed fluorescence quenching experiments, using both water-soluble and membrane-embedded quenchers. The quenching results, together with the structure, strongly support a membrane association model in which the convex, apolar face of tyrocidine's beta sheet is oriented toward the membrane interior, while the concave, polar face is presented to the aqueous phase.

PubMed: 24530898
DOI: 10.1016/j.bbamem.2014.01.033

実験手法

X-RAY DIFFRACTION (0.95 Å)