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Org Biomol Chem. 2004 Jun 21;2(12):1732-41. Epub 2004 May 25.

Inhibition of thiamin diphosphate dependent enzymes by 3-deazathiamin diphosphate.

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1
University Chemical Laboratory, Lensfield Road, Cambridge, UKCB2 1EW.

Abstract

3-Deazathiamin diphosphate (deazaTPP) and a second thiamin diphosphate (TPP) analogue having a benzene ring in place of the thiazolium ring have been synthesised. These compounds are both extremely potent inhibitors of pyruvate decarboxylase from Zymomonas mobilis; binding is competitive with TPP and is essentially irreversible even though no covalent linkage is formed. DeazaTPP binds approximately seven-fold faster than TPP and at least 25,000-fold more tightly (K(i) less than 14 pM). DeazaTPP is also a potent inhibitor of the E1 subunit of alpha-ketoglutarate dehydrogenase from E. coli and binds more than 70-fold faster than TPP. In this case slow reversal of the inhibition could be observed and a K(i) value of about 5 nM was calculated (ca. 500-fold tighter binding than TPP).

PMID:
15188040
DOI:
10.1039/b403619k
[Indexed for MEDLINE]
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