Hb Rancho Mirage [beta 143(H21)His----Asp]; a variant in the 2,3-DPG binding site showing normal oxygen affinity at physiological pH.

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.

• Authors: W F Moo-Penn, T K Hine, M H Johnson, D L Jue, S Holland, S George, A M Pierce, L A Michalski, M J McDonald
• Journal: Hemoglobin (Hemoglobin) Vol. 16 Issue 1-2 Pg. 35-44 ( 1992) ISSN: 0363-0269 [Print] England
• PMID: 1634360 (Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Diphosphoglyceric Acids
• Hemoglobins, Abnormal
• 2,3-Diphosphoglycerate
• hemoglobin Rancho Mirage
• Oxygen

Topics

• 2,3-Diphosphoglycerate
• Adolescent
• Binding Sites
• Diphosphoglyceric Acids (chemistry)
• Hemoglobins, Abnormal (metabolism)
• Humans
• Hydrogen-Ion Concentration
• Kinetics
• Male
• Oxygen (metabolism)
• Peptide Mapping