Specificity of GDP-Man:dolichyl-phosphate mannosyltransferase for the guanosine diphosphate esters of mannose analogues containing deoxy and deoxyfluoro substituents.
Guanosine diphosphate (GDP) esters of 2-deoxy-D-glucose (2dGlc), 2-deoxy-2-fluoro-D-mannose (2FMan), 3-deoxy-D-mannose (3dMan), 4-deoxy-D-mannose (4dMan) and 6-deoxy-D-mannose (6dMan) have been synthesised and tested for their ability to act as inhibitors of dolichyl phosphate mannose synthesis (enzyme: GDP-mannose:dolichyl-phosphate mannosyltransferase, EC 2.4.1.83) in chick embryo cell microsomal membranes. The following order of efficiency was found with the apparent Ki in parentheses: GDP-6dMan (0.40 microM +/- 0.15) greater than GDP-3dMan (1.0 microM +/- 0.1) = GDP-2dGlc (1.3 microM +/- 0.2) greater than GDP-4dMan (3.1 microM +/- 0.1) GDP-2FMan (15 microM +/- 0). For comparison the Km for GDP-Man was 0.52 microM +/- 0.02 and the Ki for GDP was 56 microM +/- 2. These results indicate that the 6-hydroxyl group of mannose is not crucial for enzyme-substrate recognition, whereas the 2- and 3-hydroxyls may have some involvement. The 4-hydroxyl appears to be an important determinant for enzyme-substrate recognition in this mannosyltransferase.
McDowell
W
W
Institut für Virologie, Justus-Liebig-Universität, Giessen, FRG.
Schwarz
R T
RT
D000818:Animals; D002642:Chick Embryo; D006156:Guanosine Diphosphate Sugars / Q000378:metabolism* / Q000494:pharmacology; D006600:Hexosephosphates / Q000378:metabolism*; D006602:Hexosyltransferases / Q000378:metabolism*; D006900:Hydroxylation; D007700:Kinetics; D008360:Mannosephosphates / Q000378:metabolism* / Q000494:pharmacology; D008364:Mannosyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008861:Microsomes / Q000201:enzymology; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D006156:Guanosine Diphosphate Sugars; D006600:Hexosephosphates; D008360:Mannosephosphates; D009702:Nucleoside Diphosphate Sugars; D006602:Hexosyltransferases; D008364:Mannosyltransferases; C022755:dolichyl-phosphate beta-D-mannosyltransferase