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Warfarin inhibits allosterically the reductive nitrosylation of ferric human serum heme-albumin
Warfarin inhibits allosterically the reductive nitrosylation of ferric human serum heme-albumin
- Source :
- Journal of Inorganic Biochemistry. 177:63-75
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Human serum heme-albumin (HSA-heme-Fe) displays heme-based ligand binding and (pseudo-)enzymatic properties. Here, the effect of the prototypical drug warfarin on kinetics and thermodynamics of NO binding to ferric and ferrous HSA-heme-Fe (HSA-heme-Fe(III) and HSA-heme-Fe(II), respectively) and on the NO-mediated reductive nitrosylation of the heme-Fe atom is reported; data were obtained between pH 5.5 and 9.5 at 20.0 °C. Since warfarin is a common drug, its effect on the reactivity of HSA-heme-Fe represents a relevant issue in the pharmacological therapy management. The inhibition of NO binding to HSA-heme-Fe(III) and HSA-heme-Fe(II) as well as of the NO-mediated reductive nitrosylation of the heme-Fe(III) atom by warfarin has been ascribed to drug binding to the fatty acid binding site 2 (FA2), shifting allosterically the penta-to-six coordination equilibrium of the heme-Fe atom toward the low reactive species showing the six-coordinated metal center by His146 and Tyr161 residues. These data: (i) support the role of HSA-heme-Fe in trapping NO, (ii) highlight the modulation of the heme-Fe-based reactivity by drugs, and (iii) could be relevant for the modulation of HSA functions by drugs in vivo.
- Subjects :
- 0301 basic medicine
Allostery
Ferric human serum heme-albumin
Ferrous human serum heme-albumin
Nitrogen monoxide binding
Reductive nitrosylation
Warfarin
Biochemistry
Inorganic Chemistry
Stereochemistry
Iron
Allosteric regulation
Serum Albumin, Human
Heme
Ligands
Nitric Oxide
Ferrous
03 medical and health sciences
chemistry.chemical_compound
Fatty acid binding
medicine
Humans
Reactivity (chemistry)
Settore BIO/10
Serum Albumin
chemistry.chemical_classification
030102 biochemistry & molecular biology
Nitrosylation
Hydrogen-Ion Concentration
body regions
Kinetics
030104 developmental biology
Enzyme
chemistry
embryonic structures
Thermodynamics
Ferric
Oxidation-Reduction
Protein Binding
Human
medicine.drug
Subjects
Details
- ISSN :
- 01620134
- Volume :
- 177
- Database :
- OpenAIRE
- Journal :
- Journal of Inorganic Biochemistry
- Accession number :
- edsair.doi.dedup.....2ba29a201deb29d556f1a8357f5c9dd8
- Full Text :
- https://doi.org/10.1016/j.jinorgbio.2017.08.030