The Five-To-Six-Coordination Transition of Ferric Human Serum Heme-Albumin Is Allosterically-Modulated by Ibuprofen and Warfarin: A Combined XAS and MD Study

• DOI: 10.1371/journal.pone.0104231
• Publication Date: 2014-08-25T17:51:58Z
• Authors: Carlo Meneghini; Loris Leboffe; Monica Bionducci; Gabriella Fanali; Massimiliano Meli; Giorgio Colombo; Mauro Fasano; Paolo Ascenzi; Settimio Mobilio
• Keywords: X-ray absorption spectroscopy; Human serum albumin; XANES

Human serum albumin (HSA) is involved physiologically in heme scavenging; turn, heme-albumin (HSA-heme-Fe) displays globin-like properties. Here, the allosteric effect of ibuprofen and warfarin on local atomic structure around ferric heme-Fe (heme-Fe(III)) atom HSA-heme-Fe (HSA-heme-Fe(III)) has been probed by Fe-K edge X-ray absorption spectroscopy (XAS). The quantitative analysis extended fine (EXAFS) signals modeling near (XANES) spectral features demonstrated that binding modify heme-Fe(III). Combined XAS data targeted molecular dynamics (MD) simulations provided resolution insights protein structural rearrangements required to accommodate heme-Fe(III) upon binding. In absence drugs, penta-coordinated having distorted 4+1 configuration made nitrogen atoms porphyrin ring oxygen phenoxy Tyr161 residue. MD show association secondary fatty acid (FA) site 2 (FA2) induces a reorientation domain I HSA-heme-Fe(III), this leads redirection His146 residue providing an additional bond atom, 5+1 configuration. comparison XANES spectra calculated using structures with those obtained experimentally confirms reliability proposed model. As whole, combining it possible provide reliable model coordination state understand complex transition occurring HSA-heme-Fe(III)