Inhibition kinetics of carba- and C-fucosyl analogues of GDP-fucose against fucosyltransferase V: implication for the reaction mechanism.
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.
Norris
Andrew J
AJ
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA.
Whitelegge
Julian P
JP
Strouse
M Jane
MJ
Faull
Kym F
KF
Toyokuni
Tatsushi
T
D001665:Binding Sites; D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005647:Fucosyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006154:Guanosine Diphosphate Fucose / Q000031:analogs & derivatives / Q000494:pharmacology*; D007202:Indicators and Reagents; D007700:Kinetics; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D006154:Guanosine Diphosphate Fucose; D005647:Fucosyltransferases; C435083:fucosyltransferase V