Hb Rancho Mirage [beta 143(H21)His----Asp]; a variant in the 2,3-DPG binding site showing normal oxygen affinity at physiological pH.
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.
Moo-Penn
W F
WF
Centers for Disease Control, Atlanta, GA 30333.
Hine
T K
TK
Johnson
M H
MH
Jue
D L
DL
Holland
S
S
George
S
S
Pierce
A M
AM
Michalski
L A
LA
McDonald
M J
MJ
D019794:2,3-Diphosphoglycerate; D000293:Adolescent; D001665:Binding Sites; D004163:Diphosphoglyceric Acids / Q000737:chemistry*; D006455:Hemoglobins, Abnormal / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D010449:Peptide Mapping
D004163:Diphosphoglyceric Acids; D006455:Hemoglobins, Abnormal; D019794:2,3-Diphosphoglycerate; C075789:hemoglobin Rancho Mirage; D010100:Oxygen