title: Polymerization and solubility of Ni(II)-Fe(II) hybrid Hb S.
abstract: Polymerization of half-liganded Hb S was investigated using Ni(II)-Fe(II) hybrid Hb S, in which heme in either alpha or beta s subunits is replaced by Ni (II) protoporphyrin IX. Studies on the polymerization of these hybrid hemoglobins were carried out under aerobic conditions. Both alpha 2 (Ni) beta 2s (Fe-CO) and alpha 2 (Fe-CO) beta 2s (Ni) polymerized with a distinct delay time as do native deoxy-Hb S and Ni(II) Hb S. However, the critical concentration for polymerization of half-liganded Hb S, alpha 2 (Ni) beta 2s (Fe-CO) and alpha 2 (Fe-CO) beta 2s (Ni), was 4- and 8-times higher, respectively, than that of Ni(II)-Hb S. Kinetics of polymerization of both deoxygenated hybrid hemoglobins with CO completely removed were the same, although the critical concentrations for polymerization were intermediate between those for deoxy-Hb S and Ni(II)-Hb S. These results suggest that the small tertiary conformational change associated with the doubly liganded state may be much less favorable to polymerization than the completely unliganded state of Hb S. The conformational change depends on whether alpha or beta chain is liganded. The ease of polymerization and low solubility of sickle hemoglobin is dependent not only on quaternary, but on tertiary structural changes, as well as on the substitution of Val for Glu at the beta 6 position.
authors.affiliation: Children's Hospital of Philadelphia, Department of Pediatrics, PA 19104.
authors.forename: K
authors.initials: K
authors.lastname: Adachi
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: N
authors.initials: N
authors.lastname: Shibayama
mesh_terms: D006451:Hemoglobin, Sickle / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D007700:Kinetics; D008024:Ligands; D046911:Macromolecular Substances; D009532:Nickel / Q000494:pharmacology*; D055503:Protein Multimerization; D012995:Solubility
chemical_list: D006451:Hemoglobin, Sickle; D008024:Ligands; D046911:Macromolecular Substances; D009532:Nickel; D007501:Iron