title: High-resolution crystallographic analysis of a co-operative dimeric hemoglobin.
abstract: High-resolution crystal structures of the co-operative dimeric hemoglobin from the blood clam Scapharca inaequivalvis have been determined in the unliganded (deoxy) and carbon monoxide (CO) liganded states. The deoxy structure has been refined at 1.6 A resolution to an R-factor of 0.158 and the CO structure has been refined at 1.4 A resolution to an R-factor of 0.159. These structures reveal details of the structural transitions involved in co-operative ligand binding that involve only a minor rotation of subunits but very striking tertiary changes at the interface. A small number of residues in the F-helix appear to mediate co-operativity in this simple hemoglobin. The oxygen affinity of each subunit appears to be largely dictated by the disposition of phenylalanine 97, whose side-chain packs in the heme pocket in the deoxy state but is extruded towards the interface in the CO-liganded structure. Direct involvement of the ligand-binding heme group is a novel feature of the subunit interface and appears important for intersubunit communication. Ligation alters the conformation of the heme propionate groups along with two interacting residues from the symmetry-related subunit. These two residues, lysine 96 and asparagine 100, link the heme of one subunit with the F-helix of the second subunit in such a way as to influence the ligand affinity of that subunit. The interface is highly hydrated by well-ordered water molecules that are likely to be important in the stabilization of the two structures.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605.
authors.forename: W E
authors.initials: WE
authors.lastname: Royer
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D049872:Bivalvia; D002248:Carbon Monoxide / Q000378:metabolism; D018360:Crystallography, X-Ray; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D014867:Water / Q000737:chemistry
chemical_list: D006454:Hemoglobins; D014867:Water; D002248:Carbon Monoxide; D010100:Oxygen