Mechanism of Action of Flavin-Dependent Halogenases
Rhys Barker, Yuqi Yu, Leonardo De Maria, Linus O. Johannissen, Nigel S. Scrutton
Abstract
intermediate. Here, we present the most likely mechanism for halogenation based on molecular dynamics (MD) simulations and active-site density functional theory "cluster" models of FDH PrnA in complex with its native substrate l-tryptophan, hypochlorous acid, and the FAD cofactor. MD simulations with different protonation states for key active-site residues suggest that Lys79 directs HOCl through hydrogen bonding, which is confirmed by calculations of the reaction profiles for both proposed mechanisms.
Topics & Concepts
Active siteChemistryHypochlorous acidProtonationHalogenationFlavin groupStereochemistryFlavin mononucleotideBinding siteHydrogen bondCombinatorial chemistryCatalysisMoleculeOrganic chemistryBiochemistryEnzymeIonMicrobial bioremediation and biosurfactantsAmino Acid Enzymes and MetabolismWater Treatment and Disinfection