Current mechanistic understanding of thiamin diphosphatedependent enzymatic reactions

TitleCurrent mechanistic understanding of thiamin diphosphatedependent enzymatic reactions
Publication TypeJournal Article
Year of Publication2003
AuthorsJordan, F
JournalNatural Product Reports
Volume20
Pagination184-201
Date PublishedApr
Type of ArticleReview
ISBN Number0265-0568
Accession Numberhttp://apps.isiknowledge.com/InboundService.do?Func=Frame&product=WOS&action=retrieve&SrcApp=EndNote&Init=Yes&SrcAuth=ResearchSoft&mode=FullRecord&UT=000182268900002
KeywordsACID-BASE GROUPS, ANGSTROM RESOLUTION, BENZOYLFORMATE DECARBOXYLASE, CRYSTAL-STRUCTURE, DEHYDROGENASE, DEPENDENT ENZYME, ESCHERICHIA-COLI, MULTIENZYME COMPLEXES, SUBSTRATE-ACTIVATION SITE, YEAST PYRUVATE-DECARBOXYLASE, ZYMOMONAS-MOBILIS
Abstract

The mechanism of thiamin diphosphate-dependent enzymatic reactions is discussed, concentrating on two enzymes involved in decarboxylating pyruvic acid, the yeast pyruvate decarboxylase and the pyruvate dehydrogenase multienzyme complex from Escherichia coli. The availability of high-resolution X-ray structures for several thiamin diphosphate-dependent enzymes, the use of site-specifically substituted protein variants (resulting from site-directed mutagenesis), the development of model reactions for the various putative intermediates, and the application of new mechanistic tools in solution have all contributed to a much better understanding of the role of the protein component in catalysis. Perhaps the most important advance in our understanding of these mechanisms concerns the role of the 4'-aminopyrimidine component of the coenzyme, widely ignored prior to the publication of the X-ray results. The current view is that the two aromatic rings both contribute to catalysis, perhaps carrying out an intramolecular proton transfer to initiate the various reactions, an ability that makes this coenzyme virtually unique among coenzymes.

URLhttp://apps.isiknowledge.com/InboundService.do?Func=Frame&product=WOS&action=retrieve&SrcApp=EndNote&Init=Yes&SrcAuth=ResearchSoft&mode=FullRecord&UT=000182268900002
Alternate JournalNat. Prod. Rep.