5DCH

Crystal structure of Pseudomonas aeruginosa DsbA E82I in complex with MIPS-0000851 (3-[(2-METHYLBENZYL)SULFANYL]-4H-1,2,4-TRIAZOL-4-AMINE)

5DCH の概要

• エントリーDOI: 10.2210/pdb5dch/pdb
• 関連するPDBエントリー: 2MBU 4ZL7 4ZL8 4ZL9
• 分子名称: Thiol:disulfide interchange protein DsbA, 3-[(2-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-4-amine, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: thioredoxin fold, oxidoreductase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22135.42

構造登録者

McMahon, R.M.,Martin, J.L. (登録日: 2015-08-24, 公開日: 2016-10-05, 最終更新日: 2024-11-06)

主引用文献

Mohanty, B.,Rimmer, K.,McMahon, R.M.,Headey, S.J.,Vazirani, M.,Shouldice, S.R.,Coincon, M.,Tay, S.,Morton, C.J.,Simpson, J.S.,Martin, J.L.,Scanlon, M.J.
Fragment library screening identifies hits that bind to the non-catalytic surface of Pseudomonas aeruginosa DsbA1.
PLoS ONE, 12:e0173436-e0173436, 2017

PubMed Abstract: At a time when the antibiotic drug discovery pipeline has stalled, antibiotic resistance is accelerating with catastrophic implications for our ability to treat bacterial infections. Globally we face the prospect of a future when common infections can once again kill. Anti-virulence approaches that target the capacity of the bacterium to cause disease rather than the growth or survival of the bacterium itself offer a tantalizing prospect of novel antimicrobials. They may also reduce the propensity to induce resistance by removing the strong selection pressure imparted by bactericidal or bacteriostatic agents. In the human pathogen Pseudomonas aeruginosa, disulfide bond protein A (PaDsbA1) plays a central role in the oxidative folding of virulence factors and is therefore an attractive target for the development of new anti-virulence antimicrobials. Using a fragment-based approach we have identified small molecules that bind to PaDsbA1. The fragment hits show selective binding to PaDsbA1 over the DsbA protein from Escherichia coli, suggesting that developing species-specific narrow-spectrum inhibitors of DsbA enzymes may be feasible. Structures of a co-complex of PaDsbA1 with the highest affinity fragment identified in the screen reveal that the fragment binds on the non-catalytic surface of the protein at a domain interface. This biophysical and structural data represent a starting point in the development of higher affinity compounds, which will be assessed for their potential as selective PaDsbA1 inhibitors.

PubMed: 28346540
DOI: 10.1371/journal.pone.0173436

実験手法

X-RAY DIFFRACTION (1.447 Å)