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Title: Abacavir and warfarin modulate allosterically kinetics of NO dissociation from ferrous nitrosylated human serum heme-albumin

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{sub off}) is reported. In the absence of drugs, the value of k{sub off} is (1.3 {+-} 0.2) x 10{sup -4} s{sup -1}. Abacavir and warfarin facilitate NO dissociation from HSA-heme-Fe(II)-NO, the k{sub off} value increases to (8.6 {+-} 0.9) x 10{sup -4} s{sup -1}. From the dependence of k{sub 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{sup -3} M and (6.2 {+-} 0.7) x 10{sup -5} M, respectively) were determined. The increase of k{sub 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.
Authors:
 [1] ;  [2] ;  [1] ;  [3] ;  [4] ;  [5]
  1. Department of Biology and Interdepartmental Laboratory for Electron Microscopy, University 'Roma Tre', Viale Guglielmo Marconi 446, I-00146 Roma (Italy)
  2. (Italy), E-mail: ascenzi@uniroma3.it
  3. (Italy)
  4. Department of Experimental Medicine and Biochemical Sciences, University of Roma 'Tor Vergata', Via Montpellier 1, I-00133 Roma (Italy)
  5. Department of Structural and Functional Biology, and Center of Neuroscience, University of Insubria, Via Alberto da Giussano 12, I-21052 Busto Arsizio (Vatican City State, Holy See,) (Italy)
Publication Date:
OSTI Identifier:
21143655
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 369; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2008.02.077; PII: S0006-291X(08)00350-1; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALBUMINS; BLOOD SERUM; HEME; HEMOGLOBIN; INOSITOL; LIGANDS; MYOGLOBIN; NITRIC OXIDE