2PRB

crystal structure of aminoglycoside acetyltransferase AAC(6')-Ib in complex whith coenzyme A

2PRB の概要

• エントリーDOI: 10.2210/pdb2prb/pdb
• 関連するPDBエントリー: 2PR8
• 分子名称: Aminoglycoside 6-N-acetyltransferase type Ib11, COENZYME A (3 entities in total)
• 機能のキーワード: gnat, aminoglycoside acetyltransferase, transferase
• 由来する生物種: Salmonella typhimurium
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22688.97

構造登録者

Maurice, F.,Broutin, I.,Podglajen, I.,Benas, P.,Collatz, E.,Dardel, F. (登録日: 2007-05-04, 公開日: 2008-04-08, 最終更新日: 2023-08-30)

主引用文献

Maurice, F.,Broutin, I.,Podglajen, I.,Benas, P.,Collatz, E.,Dardel, F.
Enzyme structural plasticity and the emergence of broad-spectrum antibiotic resistance.
Embo Rep., 9:344-349, 2008

PubMed Abstract: The emergence of multi-resistant pathogenic bacteria is a worldwide health issue. Recently, clinical variants of a single antibiotic-modifying acetyltransferase, AAC(6')-Ib-a variant of aminoglycoside 6'-N-acetyltransferase-have been identified that confer extended resistance to most aminoglycosides and, more surprisingly, to structurally unrelated fluoroquinolones. The corresponding gene is carried by mobile genetic elements and is present in most multi-resistant pathogenic strains, hence making it a serious threat to current therapies. Here, we report the crystal structures of both narrow- and broad-spectrum resistance variants of this enzyme, which reveal the structural basis for the emergence of extended resistance. The active site shows an important plasticity and has adapted to new substrates by a large-scale gaping process. We have also obtained co-crystals with both substrates, and with a simple transition state analogue, which provides new clues for the design of inhibitors of this resistance mechanism.

PubMed: 18292754
DOI: 10.1038/embor.2008.9

実験手法

X-RAY DIFFRACTION (1.8 Å)