Effect of bezafibrate and clofibrate on the heme-iron geometry of ferrous nitrosylated heme-human serum albumin: an EPR study.
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.
Mattu
M
M
Department of Biology, University of Rome Tre, Rome, Italy.
Vannin
A
A
Coletta
M
M
Fasano
M
M
Ascenzi
P
P
D001629:Bezafibrate / Q000494:pharmacology*; D002994:Clofibrate / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D006418:Heme / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D020836:Protein Structure, Quaternary / Q000187:drug effects; D017434:Protein Structure, Tertiary / Q000187:drug effects; D012709:Serum Albumin / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism
D000960:Hypolipidemic Agents; D012709:Serum Albumin; D006418:Heme; C027417:nitrosylprotoheme; D002994:Clofibrate; D001629:Bezafibrate