1BED

STRUCTURE OF DISULFIDE OXIDOREDUCTASE

1BED の概要

• エントリーDOI: 10.2210/pdb1bed/pdb
• 分子名称: DSBA OXIDOREDUCTASE (2 entities in total)
• 機能のキーワード: tcpg, protein disulfide isomerase, disulfide oxidoreductase, oxidoreductase
• 由来する生物種: Vibrio cholerae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20523.42

構造登録者

Hu, S.-H.,Martin, J.L. (登録日: 1996-09-16, 公開日: 1997-10-08, 最終更新日: 2024-11-13)

主引用文献

Hu, S.H.,Peek, J.A.,Rattigan, E.,Taylor, R.K.,Martin, J.L.
Structure of TcpG, the DsbA protein folding catalyst from Vibrio cholerae.
J.Mol.Biol., 268:137-146, 1997

PubMed Abstract: The efficient and correct folding of bacterial disulfide bonded proteins in vivo is dependent upon a class of periplasmic oxidoreductase proteins called DsbA, after the Escherichia coli enzyme. In the pathogenic bacterium Vibrio cholerae, the DsbA homolog (TcpG) is responsible for the folding, maturation and secretion of virulence factors. Mutants in which the tcpg gene has been inactivated are avirulent; they no longer produce functional colonisation pili and they no longer secrete cholera toxin. TcpG is thus a suitable target for inhibitors that could counteract the virulence of this organism, thereby preventing the symptoms of cholera. The crystal structure of oxidized TcpG (refined at a resolution of 2.1 A) serves as a starting point for the rational design of such inhibitors. As expected, TcpG has the same fold as E. coli DsbA, with which it shares approximately 40% sequence identity. In addition, the characteristic surface features of DsbA are present in TcpG, supporting the notion that these features play a functional role. While the overall architecture of TcpG and DsbA is similar and the surface features are retained in TcpG, there are significant differences. For example, the kinked active site helix results from a three-residue loop in DsbA, but is caused by a proline in TcpG (making TcpG more similar to thioredoxin in this respect). Furthermore, the proposed peptide binding groove of TcpG is substantially shortened compared with that of DsbA due to a six-residue deletion. Also, the hydrophobic pocket of TcpG is more shallow and the acidic patch is much less extensive than that of E. coli DsbA. The identification of the structural and surface features that are retained or are divergent in TcpG provides a useful assessment of their functional importance in these protein folding catalysts and is an important prerequisite for the design of TcpG inhibitors.

PubMed: 9149147
DOI: 10.1006/jmbi.1997.0940

実験手法

X-RAY DIFFRACTION (2 Å)