Effect of bezafibrate and clofibrate on the heme–iron geometry of ferrous nitrosylated heme–human serum albumin: an EPR study

• Published in: Journal of inorganic biochemistry 2001-04, Vol.84 (3), p.293-296
• Main Authors: Mattu, Marco, Vannini, Alessandro, Coletta, Massimo, Fasano, Mauro, Ascenzi, Paolo
• Format: Article
• Language: English
• Subjects: Bezafibrate; Bezafibrate - pharmacology; Clofibrate; Clofibrate - pharmacology; Electron Spin Resonance Spectroscopy; EPR spectroscopic properties; Ferrous nitrosylated heme–human serum albumin; Heme - analogs & derivatives; Heme - chemistry; Heme - metabolism; Heme–iron geometry; Humans; Hypolipidemic Agents - pharmacology; Molecular Structure; Protein Binding - drug effects; Protein Structure, Quaternary - drug effects; Protein Structure, Tertiary - drug effects; Serum Albumin - chemistry; Serum Albumin - drug effects; Serum Albumin - metabolism
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/S0162-0134(01)00185-4

The effect of bezafibrate (BZF) and clofibrate (CF), two therapeutic drugs displaying anticoagulant and antihyperlipoproteinemic activities, on the EPR-spectroscopic properties of ferrous nitrosylated heme–human serum albumin (HSA–heme–NO) has been investigated. In the absence of BZF and CF, HSA–heme–NO is a five-coordinate heme–iron system, characterised by an X-band EPR spectrum with a three-line splitting in the high magnetic field region. Addition of BZF and CF to HSA–heme–NO induced the transition towards a six-coordinate heme–iron species characterised by an X-band EPR spectrum with an axial geometry. These data indicate that HSA–heme–NO is a five-coordinate heme–iron system, BZF and CF acting as allosteric effectors, and show that the primary heme binding site and the CF cleft of HSA are conformationally-linked, regardless of their different location.