Sugar nucleotide recognition by Klebsiella pneumoniae UDP-D-galactopyranose mutase: Fluorinated substrates, kinetics and equilibria

J.C. Errey, M.C. Mann, S.A. Fairhurst, L. Hill, M.R. McNeil, J.H. Naismith, J.M. Percy, C. Whitfield

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.
LanguageEnglish
Pages1009-1016
Number of pages7
JournalOrganic and Biomolecular Chemistry
Volume7
Issue number5
DOIs
Publication statusPublished - 2009

Fingerprint

Intramolecular Transferases
Klebsiella
pneumonia
Uridine Diphosphate
nucleotides
Klebsiella pneumoniae
sugars
Galactose
Sugars
Nucleotides
galactose
Kinetics
kinetics
Substrates
Uridine Diphosphate Galactose
Hydroxyl Radical
Stereochemistry
stereochemistry
infectious diseases
adducts

Keywords

  • catalytic mechanism
  • chemical synthesis
  • o-antigen
  • biosynthesis
  • galactofuranose

Cite this

Errey, J. C., Mann, M. C., Fairhurst, S. A., Hill, L., McNeil, M. R., Naismith, J. H., ... Whitfield, C. (2009). Sugar nucleotide recognition by Klebsiella pneumoniae UDP-D-galactopyranose mutase: Fluorinated substrates, kinetics and equilibria. Organic and Biomolecular Chemistry, 7(5), 1009-1016. https://doi.org/10.1039/b815549f
Errey, J.C. ; Mann, M.C. ; Fairhurst, S.A. ; Hill, L. ; McNeil, M.R. ; Naismith, J.H. ; Percy, J.M. ; Whitfield, C. / Sugar nucleotide recognition by Klebsiella pneumoniae UDP-D-galactopyranose mutase: Fluorinated substrates, kinetics and equilibria. In: Organic and Biomolecular Chemistry. 2009 ; Vol. 7, No. 5. pp. 1009-1016.
@article{7a9a2b05dcbd4b07a36ea04c2687cb77,
title = "Sugar nucleotide recognition by Klebsiella pneumoniae UDP-D-galactopyranose mutase: Fluorinated substrates, kinetics and equilibria",
abstract = "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.",
keywords = "catalytic mechanism, chemical synthesis, o-antigen, biosynthesis, galactofuranose",
author = "J.C. Errey and M.C. Mann and S.A. Fairhurst and L. Hill and M.R. McNeil and J.H. Naismith and J.M. Percy and C. Whitfield",
note = "Strathprints' policy is to record up to 8 authors per publication, plus any additional authors based at the University of Strathclyde. More authors may be listed on the official publication than appear in the Strathprints' record.",
year = "2009",
doi = "10.1039/b815549f",
language = "English",
volume = "7",
pages = "1009--1016",
journal = "Organic and Biomolecular Chemistry",
issn = "1477-0520",
number = "5",

}

Errey, JC, Mann, MC, Fairhurst, SA, Hill, L, McNeil, MR, Naismith, JH, Percy, JM & Whitfield, C 2009, 'Sugar nucleotide recognition by Klebsiella pneumoniae UDP-D-galactopyranose mutase: Fluorinated substrates, kinetics and equilibria' Organic and Biomolecular Chemistry, vol. 7, no. 5, pp. 1009-1016. https://doi.org/10.1039/b815549f

Sugar nucleotide recognition by Klebsiella pneumoniae UDP-D-galactopyranose mutase: Fluorinated substrates, kinetics and equilibria. / Errey, J.C.; Mann, M.C.; Fairhurst, S.A.; Hill, L.; McNeil, M.R.; Naismith, J.H.; Percy, J.M.; Whitfield, C.

In: Organic and Biomolecular Chemistry, Vol. 7, No. 5, 2009, p. 1009-1016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Sugar nucleotide recognition by Klebsiella pneumoniae UDP-D-galactopyranose mutase: Fluorinated substrates, kinetics and equilibria

AU - Errey, J.C.

AU - Mann, M.C.

AU - Fairhurst, S.A.

AU - Hill, L.

AU - McNeil, M.R.

AU - Naismith, J.H.

AU - Percy, J.M.

AU - Whitfield, C.

N1 - Strathprints' policy is to record up to 8 authors per publication, plus any additional authors based at the University of Strathclyde. More authors may be listed on the official publication than appear in the Strathprints' record.

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - catalytic mechanism

KW - chemical synthesis

KW - o-antigen

KW - biosynthesis

KW - galactofuranose

UR - http://dx.doi.org/10.1039/b815549f

U2 - 10.1039/b815549f

DO - 10.1039/b815549f

M3 - Article

VL - 7

SP - 1009

EP - 1016

JO - Organic and Biomolecular Chemistry

T2 - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

SN - 1477-0520

IS - 5

ER -