5TNR

Crystal structure of the E153Q mutant of the CFTR inhibitory factor Cif containing the adducted 16,17-EpDPE hydrolysis intermediate

5TNR の概要

• エントリーDOI: 10.2210/pdb5tnr/pdb
• 関連するPDBエントリー: 5TNF 5TNG 5TNH 5TNL 5TNM 5TNN 5TNS
• 分子名称: CFTR inhibitory factor, (4Z,7Z,10Z,13Z,16R,17R,19Z)-16,17-dihydroxydocosa-4,7,10,13,19-pentaenoic acid (3 entities in total)
• 機能のキーワード: epoxide hydrolase, hydroxyalkyl-enzyme intermediate, hydrolase
• 由来する生物種: Pseudomonas aeruginosa (strain UCBPP-PA14)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 138104.87

構造登録者

Hvorecny, K.L.,Madden, D.R. (登録日: 2016-10-14, 公開日: 2017-10-18, 最終更新日: 2024-11-06)

主引用文献

Hvorecny, K.L.,Bahl, C.D.,Kitamura, S.,Lee, K.S.S.,Hammock, B.D.,Morisseau, C.,Madden, D.R.
Active-Site Flexibility and Substrate Specificity in a Bacterial Virulence Factor: Crystallographic Snapshots of an Epoxide Hydrolase.
Structure, 25:697-707.e4, 2017

PubMed Abstract: Pseudomonas aeruginosa secretes an epoxide hydrolase with catalytic activity that triggers degradation of the cystic fibrosis transmembrane conductance regulator (CFTR) and perturbs other host defense networks. Targets of this CFTR inhibitory factor (Cif) are largely unknown, but include an epoxy-fatty acid. In this class of signaling molecules, chirality can be an important determinant of physiological output and potency. Here we explore the active-site chemistry of this two-step α/β-hydrolase and its implications for an emerging class of virulence enzymes. In combination with hydrolysis data, crystal structures of 15 trapped hydroxyalkyl-enzyme intermediates reveal the stereochemical basis of Cif's substrate specificity, as well as its regioisomeric and enantiomeric preferences. The structures also reveal distinct sets of conformational changes that enable the active site to expand dramatically in two directions, accommodating a surprising array of potential physiological epoxide targets. These new substrates may contribute to Cif's diverse effects in vivo, and thus to the success of P. aeruginosa and other pathogens during infection.

PubMed: 28392259
DOI: 10.1016/j.str.2017.03.002

実験手法

X-RAY DIFFRACTION (1.8 Å)