title: Evidence for pH-dependent multiple conformers in iron(II) heme-human serum albumin: spectroscopic and kinetic investigation of carbon monoxide binding.
abstract: Human serum albumin (HSA), the most prominent protein in plasma, is best known for its exceptional ligand binding capacity. HSA participates in heme scavenging by binding the macrocycle at fatty acid site 1. In turn, heme endows HSA with globin-like reactivity and spectroscopic properties. A detailed pH-dependent kinetic and spectroscopic investigation of iron(II) heme-HSA and of its carbonylated form is reported here. Iron (II) heme-HSA is a mixture of a four-coordinate intermediate-spin species (predominant at pH 5.8 and 7.0), a five-coordinate high-spin form (mainly at pH 7.0), and a six-coordinate low-spin species (predominant at pH 10.0). The acidic-to-alkaline reversible transition reflects conformational changes leading to the coordination of the heme Fe(II) atom by the His146 residue via its nitrogen atom, both in the presence and in the absence of CO. The presence of several species accounts for the complex, multiexponential kinetics observed and reflects the very slow interconversion between the different species observed both for CO association to the free iron(II) heme-HSA and for CO dissociation from CO-iron(II) heme-HSA as a function of pH.
authors: Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
authors: Yu
authors: Y
authors: Cao
authors: Francesco P
authors: FP
authors: Nicoletti
authors: Giampiero
authors: G
authors: De Sanctis
authors: Alessio
authors: A
authors: Bocedi
authors: Chiara
authors: C
authors: Ciaccio
authors: Francesca
authors: F
authors: Gullotta
authors: Gabriella
authors: G
authors: Fanali
authors: Grazia R
authors: GR
authors: Tundo
authors: Alessandra
authors: A
authors: di Masi
authors: Mauro
authors: M
authors: Fasano
authors: Giulietta
authors: G
authors: Smulevich
authors: Paolo
authors: P
authors: Ascenzi
authors: Massimo
authors: M
authors: Coletta
mesh_terms: D001665:Binding Sites; D002248:Carbon Monoxide / Q000737:chemistry*; D005296:Ferrous Compounds / Q000737:chemistry*; D006418:Heme / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008958:Models, Molecular; D012709:Serum Albumin / Q000737:chemistry*; D013059:Spectrum Analysis, Raman
chemical_list: D005296:Ferrous Compounds; D012709:Serum Albumin; D006418:Heme; D002248:Carbon Monoxide