Moo-Penn W F, Hine T K, Johnson M H, Jue D L, Holland S, George S, Pierce A M, Michalski L A, McDonald M J
Centers for Disease Control, Atlanta, GA 30333.
Hemoglobin. 1992;16(1-2):35-44. doi: 10.3109/03630269209005674.
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.
在一名17岁男性中检测到血红蛋白兰乔米拉奇（Hb Rancho Mirage），并伴有轻度贫血。血红蛋白电泳显示，该变体在醋酸纤维素（pH 8.6）上的迁移率介于血红蛋白A（Hb A）和血红蛋白J之间，在枸橼酸盐琼脂（pH 6.4）上的迁移率与血红蛋白F相似。在β链的第143位发现了组氨酸（His）被天冬氨酸（Asp）取代，该残基有助于血红蛋白中阴离子2,3 - 二磷酸甘油酸（2,3-DPG）结合位点的形成。该变体在生理pH下表现出正常的氧亲和力，在碱性pH下亲和力降低。这表明变构平衡发生了微妙的变化，最有可能是由于引入了一个稳定2,3-DPG口袋的负电荷。同促效应（血红素-血红素）和异促效应（2,3-DPG和质子）均降低；这可能是β亚基羧基末端区域改变的结果。虽然组氨酸被天冬氨酸取代会被认为会合理破坏β亚基的2,3-DPG和C末端构象，但血红蛋白兰乔米拉奇的特性表明，实际上关键的C末端残基似乎没有受到重大干扰。
