pH-dependence of warfarin binding to alpha 1-acid glycoprotein (orosomucoid).
The binding of warfarin to alpha 1-acid glycoprotein (AAG) was found to increase with decreasing pH. The u.v.-visible difference spectra generated upon binding to AAG at pH 5.0 or 7.4 showed warfarin to bind as the anion. Warfarin-binding data were satisfactorily fitted to a model that incorporates the effect of pH and discriminates the association constants of the non-protonated and protonated binding site of the protein. It was shown that AAG-binding site in the protonated form had a markedly higher affinity for warfarin than the non-protonated form, with a pK value of 7.7 +/- 0.1, which is likely to be a histidine residue. Among other possible interactions, it is suggested that ligand binding to AAG involves a reinforced hydrogen bond.
Urien
S
S
INSERM, Paris, France.
Brée
F
F
Testa
B
B
Tillement
J P
JP
D000838:Anions / Q000378:metabolism; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D009961:Orosomucoid / Q000737:chemistry / Q000378:metabolism*; D013053:Spectrophotometry; D014859:Warfarin / Q000737:chemistry / Q000378:metabolism*
D000838:Anions; D009961:Orosomucoid; D014859:Warfarin