title: Structural and functional consequences of amino acid substitutions in hemoglobin as manifested in natural and artificial mutants.
abstract: Compiled data for more than 440 natural human hemoglobin mutants with single amino acid substitutions indicate that molecular properties (oxygen binding, structural stability, ease of autooxidization, etc.) of more than half of them are altered in some way and that the mode of alteration is closely related to the region within the hemoglobin molecule in which the substitution takes place. The present study gives a quantitative basis for the correlations. By means of protein engineering, including site-directed mutagenesis, several artificial mutants of human hemoglobin were prepared and their oxygen binding properties were studied to investigate the functional consequences of the amino acid substitutions which have not yet been isolated in natural mutants. These artificial mutants gave straight-forward information regarding the major factors regulating the oxygen affinity of heme and the identification of a Bohr group in the alpha chain. On the other hand the mutants, which were designed to test some hypotheses for the molecular evolution in hemoglobin, did not necessarily give the results predicted from accumulated structure-function data obtained from the study of natural mutants and X-ray crystallographic analyses.
authors.affiliation: Department of Physicochemical Physiology, Medical School, Osaka University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Imai
authors.forename: D T
authors.initials: DT
authors.lastname: Shih
authors.forename: J
authors.initials: J
authors.lastname: Tame
authors.forename: K
authors.initials: K
authors.lastname: Nagai
authors.forename: G
authors.initials: G
authors.lastname: Miyazaki
mesh_terms: D000489:Alligators and Crocodiles; D000595:Amino Acid Sequence; D000818:Animals; D006454:Hemoglobins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010100:Oxygen / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D006454:Hemoglobins; D010100:Oxygen