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 EP R-spectroscopic properties of ferrous nitrosylated heme-human serum albumin (HSA-heme-NO) has been investigated. In the absence of BZF and CF, HSA-hem e-NO is a five-coordinate hems-iron system, characterised by an X-band EPR spectrum with a three-line splitting in the high magnetic field region. Add ition of BZF and CF to HSA-heme-NO induced the transition towards a six-coo rdinate heme-iron species characterised by an X-band EPR spectrum with an a xial geometry. These data indicate that HSA-heme-NO is a five-coordinate he me-iron system, BZF and CF acting as allosteric effecters, and show that th e primary heme binding site and the CF cleft of HSA are conformationally-li nked, regardless of their different location. (C) 2001 Elsevier Science B.V . All rights reserved.