1. Hb Rancho Mirage [beta 143(H21)His----Asp]; a variant in the 2,3-DPG binding site showing normal oxygen affinity at physiological pH
- Author
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S. George, Melisenda J. McDonald, Pierce Am, S. Holland, Mary H. Johnson, Michalski La, T. K. Hine, Danny L. Jue, and Winston F. Moo-Penn
- Subjects
Male ,Hemoglobin electrophoresis ,Adolescent ,Hemoglobins, Abnormal ,Clinical Biochemistry ,Allosteric regulation ,medicine.disease_cause ,Peptide Mapping ,chemistry.chemical_compound ,Residue (chemistry) ,medicine ,Humans ,Asparagine ,Binding site ,Genetics (clinical) ,Histidine ,2,3-Diphosphoglycerate ,Mutation ,Binding Sites ,Chemistry ,Biochemistry (medical) ,Hematology ,Hydrogen-Ion Concentration ,Diphosphoglyceric Acids ,Cellulose acetate ,Oxygen ,Kinetics ,Biochemistry - Abstract
Hb Rancho Mirage was detected in a 17-year-old male in association with a mild anemia. Hemoglobin electrophoresis revealed the variant had a mobility between Hbs A and J on cellulose acetate (pH 8.6) and a mobility like Hb F on citrate agar (pH 6.4). A substitution of His----Asp was found at position 143 in the beta chain, a residue that contributes to the anionic 2,3-DPG binding site in Hb. This variant exhibited normal oxygen affinity at physiologic pH and reduced affinity at alkaline pH. This suggested a subtle shift in the allosteric equilibrium due most likely to the introduction of a negative charge that stabilized the 2,3-DPG pocket. Both homotrophic (heme-heme) and heterotropic (2,3-DPG and protons) effects were reduced; this might be a consequence of an alteration in the carboxyl terminal region of the beta-subunits. Although a His----Asp substitution would be considered to cause reasonable disruption of the 2,3-DPG and C-terminal conformation of the beta- subunits, the properties of Hb Rancho Mirage suggest that, in fact, there appear to be no major perturbation of the critical C-terminal residues.
- Published
- 1992