Phosphomethylpyrimidine Synthase (ThiC): Trapping of Five Intermediates Provides Mechanistic Insights on a Complex Radical Cascade Reaction in Thiamin Biosynthesis
Vishav Sharma, Dmytro Fedoseyenko, Sumedh Joshi, Sameh H. Abdelwahed, Tadhg P. Begley
Abstract
Phosphomethylpyrimidine synthase (ThiC) catalyzes the conversion of AIR to the thiamin pyrimidine HMP-P. This reaction is the most complex enzyme-catalyzed radical cascade identified to date, and the detailed mechanism has remained elusive. In this paper, we describe the trapping of five new intermediates that provide snapshots of the ThiC reaction coordinate and enable the formulation of a revised mechanism for the ThiC-catalyzed reaction.
Topics & Concepts
BiosynthesisChemistryATP synthaseCascadeReaction intermediateEnzymePyrimidineCascade reactionCombinatorial chemistryActive siteCatalysisStereochemistryBiochemistryChromatographyBiochemical and Molecular ResearchPorphyrin Metabolism and DisordersPneumocystis jirovecii pneumonia detection and treatment