Theoretical Characterization of the Step-by-Step Mechanism of Conversion of Leukotriene A₄ to Leukotriene B₄ Catalysed by the Enzyme Leukotriene A₄ Hydrolase.

ABSTRACT: LTA₄H is a bifunctional zinc metalloenzyme that converts leukotriene A₄ (LTA₄) into leukotriene B₄ (LTB₄), one of the most potent chemotactic agents involved in acute and chronic inflammatory diseases. In this reaction, LTA₄H acts as an epoxide hydrolase with a unique and fascinating mechanism, which includes the stereoselective attachment of one water molecule to the carbon backbone of LTA₄ several methylene units away from the epoxide moiety. By combining Molecular Dynamics simulations and Quantum Mechanics/Molecular Mechanics calculations, we obtained a very detailed molecular picture of the different consecutive steps of that mechanism. By means of a rather unusual 1,7-nucleophilic substitution through a clear

SUBMITTER: Canyelles-Nino M 

PROVIDER: S-EPMC8954237 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature