3AOB

Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket

3AOB の概要

• エントリーDOI: 10.2210/pdb3aob/pdb
• 関連するPDBエントリー: 3AOA 3AOC 3AOD
• 分子名称: Acriflavine resistance protein B, RIFAMPICIN (3 entities in total)
• 機能のキーワード: membrane protein, inner membrane, membrane protein-antibiotic complex, membrane protein/antibiotic
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cell inner membrane ; Multi- pass membrane protein : P31224
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 343476.17

構造登録者

Nakashima, R.,Sakurai, K.,Yamaguchi, A. (登録日: 2010-09-23, 公開日: 2011-11-30, 最終更新日: 2023-11-01)

主引用文献

Nakashima, R.,Sakurai, K.,Yamasaki, S.,Nishino, K.,Yamaguchi, A.
Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket
Nature, 480:565-569, 2011

PubMed Abstract: AcrB and its homologues are the principal multidrug transporters in Gram-negative bacteria and are important in antibiotic drug tolerance. AcrB is a homotrimer that acts as a tripartite complex with the outer membrane channel TolC and the membrane fusion protein AcrA. Minocycline and doxorubicin have been shown to bind to the phenylalanine cluster region of the binding monomer. Here we report the crystal structures of AcrB bound to the high-molecular-mass drugs rifampicin and erythromycin. These drugs bind to the access monomer, and the binding sites are located in the proximal multisite binding pocket, which is separated from the phenylalanine cluster region (distal pocket) by the Phe-617 loop. Our structures indicate that there are two discrete multisite binding pockets along the intramolecular channel. High-molecular-mass drugs first bind to the proximal pocket in the access state and are then forced into the distal pocket in the binding state by a peristaltic mechanism involving subdomain movements that include a shift of the Phe-617 loop. By contrast, low-molecular-mass drugs, such as minocycline and doxorubicin, travel through the proximal pocket without specific binding and immediately bind to the distal pocket. The presence of two discrete, high-volume multisite binding pockets contributes to the remarkably broad substrate recognition of AcrB.

PubMed: 22121023
DOI: 10.1038/nature10641

実験手法

X-RAY DIFFRACTION (3.35 Å)