2MC0

Structural Basis of a Thiopeptide Antibiotic Multidrug Resistance System from Streptomyces lividans:Nosiheptide in Complex with TipAS

2MC0 の概要

• エントリーDOI: 10.2210/pdb2mc0/pdb
• 関連するPDBエントリー: 1NY9 2mbz
• NMR情報: BMRB: 19422
• 関連するBIRD辞書のPRD_ID: PRD_001172
• 分子名称: HTH-type transcriptional activator TipA, nosiheptide, 4-(hydroxymethyl)-3-methyl-1H-indole-2-carboxylic acid (3 entities in total)
• 機能のキーワード: bacterial protein, streptomyces lividans, transcriptional activation, tipas-nosiheptide complex, transcriptional activator-antibiotic complex, protein/thiopeptide, multidrug recognition, transcription activator-antibiotic complex, transcription activator/antibiotic
• 由来する生物種: Streptomyces lividans; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 17986.64

構造登録者

Habazettl, J.,Allan, M.G.,Jensen, P.,Sass, H.,Grzesiek, S. (登録日: 2013-08-12, 公開日: 2014-12-10, 最終更新日: 2023-11-15)

主引用文献

Habazettl, J.,Allan, M.,Jensen, P.R.,Sass, H.J.,Thompson, C.J.,Grzesiek, S.
Structural basis and dynamics of multidrug recognition in a minimal bacterial multidrug resistance system
Proc.Natl.Acad.Sci.USA, 111:E5498-E5507, 2014

PubMed Abstract: TipA is a transcriptional regulator found in diverse bacteria. It constitutes a minimal autoregulated multidrug resistance system against numerous thiopeptide antibiotics. Here we report the structures of its drug-binding domain TipAS in complexes with promothiocin A and nosiheptide, and a model of the thiostrepton complex. Drug binding induces a large transition from a partially unfolded to a globin-like structure. The structures rationalize the mechanism of promiscuous, yet specific, drug recognition: (i) a four-ring motif present in all known TipA-inducing antibiotics is recognized specifically by conserved TipAS amino acids; and (ii) the variable part of the antibiotic is accommodated within a flexible cleft that rigidifies upon drug binding. Remarkably, the identified four-ring motif is also the major interacting part of the antibiotic with the ribosome. Hence the TipA multidrug resistance mechanism is directed against the same chemical motif that inhibits protein synthesis. The observed identity of chemical motifs responsible for antibiotic function and resistance may be a general principle and could help to better define new leads for antibiotics.

PubMed: 25489067
DOI: 10.1073/pnas.1412070111

実験手法

SOLUTION NMR