Inhibition kinetics of carba- and C-fucosyl analogues of GDP-fucose against fucosyltransferase V: implication for the reaction mechanism

Andrew J Norris; Julian P Whitelegge; M Jane Strouse; Kym F Faull; Tatsushi Toyokuni

doi:10.1016/j.bmcl.2003.12.003

Inhibition kinetics of carba- and C-fucosyl analogues of GDP-fucose against fucosyltransferase V: implication for the reaction mechanism

Bioorg Med Chem Lett. 2004 Feb 9;14(3):571-3. doi: 10.1016/j.bmcl.2003.12.003.

Authors

Andrew J Norris¹, Julian P Whitelegge, M Jane Strouse, Kym F Faull, Tatsushi Toyokuni

Affiliation

¹ Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA.

PMID: 14741245
DOI: 10.1016/j.bmcl.2003.12.003

Abstract

Inhibition kinetics of two isosteric analogues of GDP-fucose (GDP-Fuc) were investigated against fucosyltransferase V using electrospray ionization mass spectrometry coupled to multiple reaction monitoring. The carba-Fuc analogue was found to be a competitive inhibitor with a K(i) value of 67.1+/-9.8 microM, similar to the K(m) value for GDP-Fuc (50.4+/-5.5 microM), while the C-Fuc analogue exhibited significantly weak competitive inhibition with a K(i) value of 889+/-93 microM.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Binding Sites
Binding, Competitive
Enzyme Inhibitors / pharmacology*
Fucosyltransferases / antagonists & inhibitors*
Fucosyltransferases / metabolism
Guanosine Diphosphate Fucose / analogs & derivatives
Guanosine Diphosphate Fucose / pharmacology*
Indicators and Reagents
Kinetics
Molecular Structure
Spectrometry, Mass, Electrospray Ionization
Substrate Specificity

Substances

Enzyme Inhibitors
Indicators and Reagents
Guanosine Diphosphate Fucose
Fucosyltransferases
fucosyltransferase V