2HQ5

Crystal structure of multidrug binding protein QacR from Staphylococcus aureus cocrystallized with compound DB359

2HQ5 の概要

• エントリーDOI: 10.2210/pdb2hq5/pdb
• 関連するPDBエントリー: 1JT6 1RKW 1RPW 2DTZ
• 分子名称: HTH-type transcriptional regulator qacR, SULFATE ION (3 entities in total)
• 機能のキーワード: multidrug recognition, db359, qacr, multidrug binding protein, transcription
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 93276.97

構造登録者

Brooks, B.E.,Brennan, R.G. (登録日: 2006-07-18, 公開日: 2007-07-17, 最終更新日: 2023-10-25)

主引用文献

Brooks, B.E.,Piro, K.M.,Brennan, R.G.
Multidrug-Binding Transcription Factor QacR Binds the Bivalent Aromatic Diamidines DB75 and DB359 in Multiple Positions
J.Am.Chem.Soc., 129:8389-8395, 2007

PubMed Abstract: Staphylococcus aureus QacR is a multidrug-binding transcription repressor. Crystal structures of multiple QacR-drug complexes reveal that these toxins bind in a large pocket, which is composed of smaller overlapping "minipockets". Stacking, van der Waals, and ionic interactions are common features of binding, whereas hydrogen bonds are limited. Pentamidine, a bivalent aromatic diamidine, interacts with QacR differently as one positively charged benzamidine moiety is neutralized by the dipoles of side-chain and peptide backbone oxygens rather than a formal negative charge from proximal acidic residues. To understand the binding mechanisms of other bivalent benzamidines, we determined the crystal structures of the QacR-DB75 and QacR-DB359 complexes and measured their binding affinities. Although these rigid aromatic diamidines bind with low-micromolar affinities, they do not use single, discrete binding modes. Such promiscuous binding underscores the intrinsic chemical redundancy of the QacR multidrug-binding pocket. Chemical redundancy is likely a hallmark of all multidrug-binding pockets, yet it is utilized by only a subset of drugs, which, for QacR, so far appears to be limited to chemically rigid, bivalent compounds.

PubMed: 17567017
DOI: 10.1021/ja072576v

実験手法

X-RAY DIFFRACTION (2.8 Å)