4WF4

Crystal structure of E.Coli DsbA co-crystallised in complex with compound 4

4WF4 の概要

• エントリーDOI: 10.2210/pdb4wf4/pdb
• 関連するPDBエントリー: 1FVK 4WET 4WEY 4WF5
• 分子名称: Thiol:disulfide interchange protein, 1,2-ETHANEDIOL, 4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylic acid, ... (4 entities in total)
• 機能のキーワード: disulfide oxidoreductase, redox protein, dsba, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Escherichia coli BL21(DE3)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42659.38

構造登録者

Adams, L.A.,Sharma, P.,Mohanty, B.,Ilyichova, O.V.,Mulcair, M.D.,Williams, M.L.,Gleeson, E.C.,Totsika, M.,Doak, B.C.,Caria, S.,Rimmer, K.,Shouldice, S.R.,Vazirani, M.,Headey, S.J.,Plumb, B.R.,Martin, J.L.,Heras, B.,Simpson, J.S.,Scanlon, M.J. (登録日: 2014-09-12, 公開日: 2015-01-21, 最終更新日: 2024-10-16)

主引用文献

Adams, L.A.,Sharma, P.,Mohanty, B.,Ilyichova, O.V.,Mulcair, M.D.,Williams, M.L.,Gleeson, E.C.,Totsika, M.,Doak, B.C.,Caria, S.,Rimmer, K.,Horne, J.,Shouldice, S.R.,Vazirani, M.,Headey, S.J.,Plumb, B.R.,Martin, J.L.,Heras, B.,Simpson, J.S.,Scanlon, M.J.
Application of Fragment-Based Screening to the Design of Inhibitors of Escherichia coli DsbA.
Angew.Chem.Int.Ed.Engl., 54:2179-2184, 2015

PubMed Abstract: The thiol-disulfide oxidoreductase enzyme DsbA catalyzes the formation of disulfide bonds in the periplasm of Gram-negative bacteria. DsbA substrates include proteins involved in bacterial virulence. In the absence of DsbA, many of these proteins do not fold correctly, which renders the bacteria avirulent. Thus DsbA is a critical mediator of virulence and inhibitors may act as antivirulence agents. Biophysical screening has been employed to identify fragments that bind to DsbA from Escherichia coli. Elaboration of one of these fragments produced compounds that inhibit DsbA activity in vitro. In cell-based assays, the compounds inhibit bacterial motility, but have no effect on growth in liquid culture, which is consistent with selective inhibition of DsbA. Crystal structures of inhibitors bound to DsbA indicate that they bind adjacent to the active site. Together, the data suggest that DsbA may be amenable to the development of novel antibacterial compounds that act by inhibiting bacterial virulence.

PubMed: 25556635
DOI: 10.1002/anie.201410341

実験手法

X-RAY DIFFRACTION (1.7 Å)