title: Reactivity of the human hemoglobin "dark side".
abstract: Ligand binding to the heme distal side is a paradigm of biochemistry. However, X-ray crystallographic studies highlighted the possibility that O(2) and NO(2) (-) may bind to the proximal heme side of ferrous human hemoglobin (Hb) α-chains complexed with the α-hemoglobin stabilizing protein and to ferric human hemoglobin β-chains, respectively. Strikingly, the role generally played by the proximal HisF8 residue is played by the distal HisE7 side chain forming the trans axial ligand of the heme-Fe atom. This: i) brings to light that Hb may utilize both heme distal and proximal sides for ligand discrimination, ii) draws attention to the nonequivalence of α- and β-chains, and iii) highlights the possibility that partially unfolded Hb derivatives may display transient ligand-binding properties different from those of the native globin.
authors.affiliation: Laboratorio Interdipartimentale di Microscopia Elettronica, Università Roma Tre, Roma, Italy. ascenzi@uniroma3.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Loris
authors.initials: L
authors.lastname: Leboffe
authors.forename: Fabio
authors.initials: F
authors.lastname: Polticelli
mesh_terms: D006418:Heme / Q000737:chemistry; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D009569:Nitric Oxide; D009585:Nitrogen Dioxide / Q000737:chemistry; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry*
chemical_list: D006454:Hemoglobins; D021122:Protein Subunits; D009569:Nitric Oxide; D006418:Heme; D009585:Nitrogen Dioxide; D010100:Oxygen