Molecular recognition in the binding of vitamin B12 by the cobalamin-specific Intrinsic Factor.
Equilibrium constants (given as log K/M-1) have been determined at pH 7.4 and 4 degrees C for binding by porcine Intrinsic Factor (B12-binding protein from the gut, specific for the 'cobalamin' series of Co corrinoids) of vitamin B12 or cyanocobalamin (10.5), cyanocobinamide, alpha-ribazole and alpha-ribazole-phosphate (main fragments produced by cleaving off the 'cobalamin' side-chain, all less than or equal to 3), and cyanocobinamide in the presence of greater than or equal to 10(-9) M ribazole (5.6 and independent of ribazole concentration), i.e. ribazole catalyses the binding of the cobinamide. It is proposed that the specificity of Intrinsic Factor for the cobalamins depends on the presence of the ribazole fragment in the cobalamin side-chain to promote an essential change in conformation before the corrinoid fragment can be bound.
Andrews
E R
ER
Department of Chemistry, University of Surrey, Guildford, UK.
Pratt
J M
JM
Brown
K L
KL
D000818:Animals; D001667:Binding, Competitive; D007437:Intrinsic Factor / Q000378:metabolism*; D007700:Kinetics; D015394:Molecular Structure; D011485:Protein Binding; D013552:Swine; D014805:Vitamin B 12 / Q000031:analogs & derivatives / Q000378:metabolism*
D007437:Intrinsic Factor; D014805:Vitamin B 12