title: Ligand binding to symmetrical FeZn hybrids of variants of human HbA with modifications in the alpha1-beta2 interface.
abstract: The equilibria of oxygen binding to and kinetics of CO combination with the symmetrical iron-zinc hybrids of a series of variants of human adult hemoglobin A have been measured at pH 7 in the presence of inositol hexaphosphate (IHP). In addition, the kinetics of CO combination have also been measured in the absence of IHP. The hybrids have the heme groups of either the alpha or the beta subunits replaced by zinc protoporphyrin IX, which is unable to bind a ligand and is a good model for permanently deoxygenated heme. The variants examined involve residues located in the alpha1beta2 interface of the hemoglobin tetramer. Alterations of residues located in the hinge region of the interface are found to affect the properties of both the alpha and the beta subunits of the protein. In contrast, alterations of residues in the switch region of the interface have substantial effects only on the mutant subunit and are poorly communicated to the normal partner subunit. When the logarithms of the rate constants for the combination of the first CO molecule with a single subunit in the presence of IHP are analyzed as functions of the logarithms of the dissociation equilibrium constants for the binding of the first oxygen under the same conditions, a linear relationship is found. The relationship is somewhat different for the alpha and beta subunits, consistent with the well-known differences in the geometries of their ligand binding sites.
authors.affiliation: Department of Medicine, University at Buffalo, VA Western New York Healthcare System, Building 20, 3495 Bailey Avenue, Buffalo, New York 14215, USA.
authors.forename: Hilda L
authors.initials: HL
authors.lastname: Hui
authors.forename: Laura D
authors.initials: LD
authors.lastname: Kwiatkowski
authors.forename: Ellen
authors.initials: E
authors.lastname: Karasik
authors.forename: Judith E
authors.initials: JE
authors.lastname: Colby
authors.forename: Robert W
authors.initials: RW
authors.lastname: Noble
mesh_terms: D002248:Carbon Monoxide / Q000378:metabolism; D006441:Hemoglobin A / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D015032:Zinc / Q000378:metabolism*
chemical_list: D008024:Ligands; D002248:Carbon Monoxide; D006441:Hemoglobin A; D007501:Iron; D015032:Zinc; D010100:Oxygen