PMID: 9655906Jul 10, 1998Paper

Sixty years of thiamin diphosphate biochemistry

Biochimica Et Biophysica Acta
A Schellenberger

Abstract

The mechanism of ThDP enzymes originates in the anionic (ylid) structure of the coenzyme. On the other hand, no ylid species (as permanently existing structure) could be detected by 13C2-NMR studies with PDC (yeast), when the cofactor binds to the active site. Therefore, the rate of ylid formation as the first step of the catalytic mechanism distinguishes decisively the power (kcat) of all ThDP enzymes. 2H/1H-exchange experiments with PDC, TK, PDH and POX have shown that within the active center of ThDP enzymes (under native pH conditions!) the aminopyrimidine part generates the essential ylid structure by enhancing the dissociation rate (acidity) of the C2-H bond up to 4-6 orders of magnitude. Moreover, it could be proved that the mechanism of substrate activation of PDC (yeast) is also connected directly with the C2-H activation by the aminopyrimidine part. Experiments with analogs of ThDP or modified apoenzymes (via site-directed mutagenesis) have shown that this mechanism requires as essential elements a hydrogen bond between the pyrimidine N1' atom and a conserved Glu side chain of the different apoenzymes as well as the (evolutionary conserved) V-conformation. The latter positions the 4'-amino group in direct (functional)...Continue Reading

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Citations

Feb 14, 2012·Journal of Molecular Modeling·Ewa D RaczyńskaTomasz M Stępniewski
Jul 6, 2007·Plant Molecular Biology·Imad AjjawiDavid K Shintani
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