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

Paolo Ascenzi, Francesco Imperi, Massimo Coletta, Mauro Fasano

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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., koff) is reported. In the absence of drugs, the value of koff is (1.3 ± 0.2) × 10-4 s-1. Abacavir and warfarin facilitate NO dissociation from HSA-heme-Fe(II)-NO, the koff value increases to (8.6 ± 0.9) × 10-4 s-1. From the dependence of koff 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) × 10-3 M and (6.2 ± 0.7) × 10-5 M, respectively) were determined. The increase of koff 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.

Original languageEnglish
Pages (from-to)686-691
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume369
Issue number2
DOIs
Publication statusPublished - May 2 2008

Fingerprint

Warfarin
Heme
Serum Albumin
Albumins
Kinetics
Stabilization
Ligands
abacavir
Atoms
Scavenging
Equilibrium constants
Pharmaceutical Preparations
Modulation
Derivatives

Keywords

  • Abacavir
  • Allostery
  • Drug-dependent denitrosylation kinetics
  • Ferrous nitrosylated human serum heme-albumin
  • Warfarin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Abacavir and warfarin modulate allosterically kinetics of NO dissociation from ferrous nitrosylated human serum heme-albumin. / Ascenzi, Paolo; Imperi, Francesco; Coletta, Massimo; Fasano, Mauro.

In: Biochemical and Biophysical Research Communications, Vol. 369, No. 2, 02.05.2008, p. 686-691.

Research output: Contribution to journalArticle

Ascenzi, Paolo ; Imperi, Francesco ; Coletta, Massimo ; Fasano, Mauro. / Abacavir and warfarin modulate allosterically kinetics of NO dissociation from ferrous nitrosylated human serum heme-albumin. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 369, No. 2. pp. 686-691.
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AB - 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., koff) is reported. In the absence of drugs, the value of koff is (1.3 ± 0.2) × 10-4 s-1. Abacavir and warfarin facilitate NO dissociation from HSA-heme-Fe(II)-NO, the koff value increases to (8.6 ± 0.9) × 10-4 s-1. From the dependence of koff 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) × 10-3 M and (6.2 ± 0.7) × 10-5 M, respectively) were determined. The increase of koff 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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