Hvorecny_2017_Structure_25_697

Reference

Title : Active-Site Flexibility and Substrate Specificity in a Bacterial Virulence Factor: Crystallographic Snapshots of an Epoxide Hydrolase - Hvorecny_2017_Structure_25_697
Author(s) : Hvorecny KL , Bahl CD , Kitamura S , Lee KSS , Hammock BD , Morisseau C , Madden DR
Ref : Structure , 25 :697 , 2017
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 alpha/beta-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.
ESTHER : Hvorecny_2017_Structure_25_697
PubMedSearch : Hvorecny_2017_Structure_25_697
PubMedID: 28392259
Gene_locus related to this paper: pseae-PA2934

Related information

Gene_locus related to this paper: pseae-PA2934

Citations formats

Hvorecny KL, Bahl CD, Kitamura S, Lee KSS, Hammock BD, Morisseau C, Madden DR (2017)
Active-Site Flexibility and Substrate Specificity in a Bacterial Virulence Factor: Crystallographic Snapshots of an Epoxide Hydrolase
Structure 25 :697

Hvorecny KL, Bahl CD, Kitamura S, Lee KSS, Hammock BD, Morisseau C, Madden DR (2017)
Structure 25 :697