Experimental observation of thiamin diphosphate-bound intermediates on enzymes and mechanistic information derived from these observations

TitleExperimental observation of thiamin diphosphate-bound intermediates on enzymes and mechanistic information derived from these observations
Publication TypeJournal Article
Year of Publication2005
AuthorsJordan, F, Nemeria NS
JournalBioorganic Chemistry
Volume33
Pagination190-215
Date PublishedJun
Type of ArticleReview
ISBN Number0045-2068
Accession Numberhttp://apps.isiknowledge.com/InboundService.do?Func=Frame&product=WOS&action=retrieve&SrcApp=EndNote&Init=Yes&SrcAuth=ResearchSoft&mode=FullRecord&UT=000229463100006
Keywords1 ',4 '-imino tautomer, 2.3 ANGSTROM RESOLUTION, ACID-BASE GROUPS, alpha-hydroxyethylthiamin diphosphate, ALPHA-KETOACID DEHYDROGENASE, BENZOYLFORMATE DECARBOXYLASE, C2, C2 alpha-carbanion or enamine, C2 alpha-lactylthiamin, circular dichroism, COMPLEX, CRYSTAL-STRUCTURE, DEHYDROGENASE, DEPENDENT, DIPHOSPHATE, ENZYMES, ESCHERICHIA-COLI, FERREDOXIN OXIDOREDUCTASE, FREE-RADICAL, INTERMEDIATE, MULTIENZYME COMPLEXES, pyruvate dehydrogenase, THIAMIN DIPHOSPHATE, YEAST PYRUVATE DECARBOXYLASE, ylide/C2-carbanion
Abstract

Thiamin diphosphate (ThDP), the vitamin B1 coenzyme, is an excellent representative of coenzymes, which carry out electrophilic catalysis by forming a covalent complex with their substrates. The function of ThDP is to greatly increase the acidity of two carbon acids by stabilizing their conjugate bases, the ylide/C2-carbanion of the thiazolium ring and the C2 alpha-carbanion (or enamine) once the substrate binds to ThDP. In recent years, several ThDP-bound intermediates on such pathways have been characterized by both solution and solid-state (X-ray) methods. Prominent among these advances are X-ray crystallographic results identifying both oxidative and non-oxidative intermediates, rapid chemical quench followed by NMR detection of a several intermediates which are stable under acidic conditions, and circular dichroism detection of the 1',4'-imino tautomer of ThDP in some of the intermediates. Some of these methods also enable the investigator to determine the rate-limiting step in the complex series of steps. (c) 2005 Elsevier Inc. All rights reserved.

URLhttp://apps.isiknowledge.com/InboundService.do?Func=Frame&product=WOS&action=retrieve&SrcApp=EndNote&Init=Yes&SrcAuth=ResearchSoft&mode=FullRecord&UT=000229463100006
Alternate JournalBioorganic Chem.