| 18307975 |
Ascenzi P, Imperi F, Coletta M, Fasano M: Abacavir and warfarin modulate allosterically kinetics of NO dissociation from ferrous nitrosylated human serum heme-albumin. Biochem Biophys Res Commun. 2008 May 2;369(2):686-91. Epub 2008 Feb 26.
Human serum albumin (HSA) participates to heme scavenging, in turn HSA-heme binds gaseous diatomic ligands at the heme-Fe-atom. Here, the effect of abacavir and warfarin on denitrosylation kinetics of HSA-heme-Fe (II)-NO (i.e., k (off)) is reported. In the absence of drugs, the value of k (off) is (1.3+/-0.2) x 10 (-4) s (-1). Abacavir and warfarin facilitate NO dissociation from HSA-heme-Fe (II)-NO, the k (off) value increases to (8.6+/-0.9) x 10 (-4) s (-1). From the dependence of k (off) on the drug concentration, values of the dissociation equilibrium constant for the abacavir and warfarin binding to HSA-heme-Fe (II)-NO (i.e., K=(1.2+/-0.2) x 10 (-3) M and (6.2+/-0.7) x 10 (-5) M, respectively) were determined. The increase of k (off) values reflects the stabilization of the basic form of HSA-heme-Fe by ligands (e.g., abacavir and warfarin) that bind to Sudlow's site I. This event parallels the stabilization of the six-coordinate derivative of the HSA-heme-Fe (II)-NO atom. Present data highlight the allosteric modulation of HSA-heme-Fe (II) reactivity by heterotropic effectors. |
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