Sugar nucleotide recognition by Klebsiella pneumoniae UDP-D-galactopyranose mutase: fluorinated substrates, kinetics and equilibria.
Org Biomol Chem
; 7(5): 1009-16, 2009 Mar 07.
Article
em En
| MEDLINE
| ID: mdl-19225684
A series of selectively fluorinated and other substituted UDP-D-galactose derivatives have been evaluated as substrates for Klebsiella pneumoniae UDP-D-galactopyranose mutase. This enzyme, which catalyses the interconversion of the pyranose and furanose forms of galactose as its UDP adduct, is a prospective drug target for a variety of microbial infections. We show that none of the 2''-, 3''- or 6''-hydroxyl groups of UDP-D-galactopyranose are essential for substrate binding and turnover. However, steric factors appear to play an important role in limiting the range of substitutions that can be accommodated at C-2'' and C-6'' of the sugar nucleotide substrate. Attempts to invert the C-2'' stereochemistry from equatorial to axial, changing D-galacto- to D-talo-configuration, in an attempt to exploit the higher percentage of furanose at equilibrium in the talo-series, met with no turnover of substrate.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transferases Intramoleculares
/
Klebsiella pneumoniae
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article