3PI6

Crystal structure of the CFTR inhibitory factor Cif with the H177Y mutation

3PI6 の概要

• エントリーDOI: 10.2210/pdb3pi6/pdb
• 関連するPDBエントリー: 3KD2 3KDA
• 分子名称: hydrolase (2 entities in total)
• 機能のキーワード: alpha/beta hydrolase, epoxide hydrolase, secreted, hydrolase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 136758.91

構造登録者

Bahl, C.D.,Madden, D.R. (登録日: 2010-11-05, 公開日: 2011-09-21, 最終更新日: 2024-10-30)

主引用文献

Bahl, C.D.,Madden, D.R.
Pseudomonas aeruginosa Cif defines a distinct class of alpha/beta epoxide hydrolases utilizing a His/Tyr ring-opening pair.
Protein Pept.Lett., 19:186-193, 2012

PubMed Abstract: The Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen that secretes a multitude of virulence factors during the course of infection. Among these is Cif, an epoxide hydrolase (EH) that reduces the functional localization of the cystic fibrosis transmembrane conductance regulator in epithelial cells. In addition to being the first reported EH virulence factor, Cif possesses unique sequence deviations from canonical EH motifs. Foremost among these is the substitution of a histidine for the first epoxide ring-opening tyrosine in the active site. To test the functional equivalence of Tyr and His side chains at this position, we have generated the mutant Cif-H177Y. Structural analysis confirms that both the WT His and mutant Tyr side chains can be accommodated without large-scale conformational changes. However, the Tyr mutant is functionally inactive. Based on a detailed analysis of the structure of the Tyr mutant, it appears that Cif's main-chain conformation imposes a functional requirement for a His at this position. Comparison with canonical EH structures reveals additional conformational differences, which are coupled to divergent sequence characteristics. When used to probe the genomes of other opportunistic pathogens, these sequence-structure criteria uncover candidate sequences that appear to form a distinct subfamily of Cif-like epoxide hydrolases characterized by a conserved His/Tyr ring-opening pair.

PubMed: 21933119

実験手法

X-RAY DIFFRACTION (1.5 Å)