Human serum albumin (HSA), the most abundant protein in human plasma, could be considered as a prototypic monomeric allosteric protein, since the ligand-dependent conformational adaptability of HSA spreads beyond the immediate proximity of the binding site(s). As a matter of fact, HSA is a major transport protein in the bloodstream and the regulation of the functional allosteric interrelationships between the different binding sites represents a fundamental information for the knowledge of its transport function. Here, kinetics and thermodynamics of the allosteric modulation: (i) of carbon monoxide (CO) binding to ferrous human serum heme-albumin (HSA-heme-Fe(II)) by warfarin (WF), and (ii) of WF binding to HSA-heme-Fe(II) by CO are reported. All data were obtained at pH 7.0 and 25°C. Kinetics of CO and WF binding to the FA1 and FA7 sites of HSA-heme-Fe(II), respectively, follows a multi-exponential behavior (with the same relative percentage for the two ligands). This can be accounted for by the existence of multiple conformations and/or heme-protein axial coordination forms of HSA-heme-Fe(II). The HSA-heme-Fe(II) populations have been characterized by resonance Raman spectroscopy, indicating the coexistence of different species characterized by four-, five- and six-coordination of the heme-Fe atom. As a whole, these results suggest that: (i) upon CO binding a conformational change of HSA-heme-Fe(II) takes place (likely reflecting the displacement of an endogenous ligand by CO), and (ii) CO and/or WF binding brings about a ligand-dependent variation of the HSA-heme-Fe(II) population distribution of the various coordinating species. The detailed thermodynamic and kinetic analysis here reported allows a quantitative description of the mutual allosteric effect of CO and WF binding to HSA-heme-Fe(II).
Bocedi A, De Sanctis G, Ciaccio C, Tundo GR, Di Masi A, Fanali G, et al. (2013). Reciprocal allosteric modulation of carbon monoxide and warfarin binding to ferrous human serum heme-albumin. PLOS ONE, 8(3) [10.1371/journal.pone.0058842.].
|Titolo:||Reciprocal allosteric modulation of carbon monoxide and warfarin binding to ferrous human serum heme-albumin.|
|Data di pubblicazione:||2013|
|Citazione:||Bocedi A, De Sanctis G, Ciaccio C, Tundo GR, Di Masi A, Fanali G, et al. (2013). Reciprocal allosteric modulation of carbon monoxide and warfarin binding to ferrous human serum heme-albumin. PLOS ONE, 8(3) [10.1371/journal.pone.0058842.].|
|Appare nelle tipologie:||1.1 Articolo in rivista|