Hemoglobin McKees Rocks (alpha2beta2145Tyr leads to Term). A human "nonsense" mutation leading to a shortened beta-chain.
Hemoglobin McKees Rocks (alpha2beta2145Tyr leads to Term). A human "nonsense" mutation leading to a shortened beta-chain.
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血红蛋白 McKees Rocks（alpha2beta2145Tyr 导致 Term）。
DOI：
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发表时间：
1976
影响因子：
15.9
通讯作者：
W. Anderson
中科院分区：
文献类型：
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作者：
R. Winslow;M. Swenberg;E. Gross;P. Chervenick;R. R. Buchman;W. Anderson
人类多肽链提前终止的第一个例子是Hb麦基斯岩，β 145 Tyr导致Term，在一个高加索家族的红细胞增多症成员中发现。Tyr β 145的密码子显然发生了点突变，从UAU变为“无义”密码子UAA或UAG，导致多肽链缩短，羧基末端氨基酸为Lys 144。这一结构结论的证据是，从异常β链的“指纹”中没有胰蛋白酶肽β T-15，发现了C-末端赖氨酸，以及这种变体血红蛋白的功能特性与由羧肽酶A消化正常人血红蛋白产生的des Tyr（145）-His（146）β血红蛋白的功能特性之间的相似性。Hb麦基斯岩具有明显异常的性质：其氧亲和力是迄今为止描述的人类变体中最高的;其玻尔效应降低;缺乏亚基协同性;并且不受2，3-二磷酸甘油酸的影响。这些属性可能是T四级构象的稳定性降低的后果，并在强变构效应肌醇六磷酸的存在下部分恢复。
The first example of the premature termination of a polypeptide chain in man appears to be Hb McKees Rocks, beta145 Tyr leads to Term, discovered in polycythemic members of a Caucasian family. Point mutation has apparently occurred at the codon for Tyr beta145 from UAU to a "nonsense" codon, UAA or UAG, resulting in a shortened polypeptide chain with Lys 144 as its carboxyl-terminal amino acid. Evidence for this structural conclusion is the absence of tryptic peptide betaT-15 from "fingerprints" of the abnormal beta-chain, the finding of C-terminal Lys, and the similarity between the functional properties of this variant hemoglobin and those of des Tyr (145)-His(146)beta hemoglobin resulting from carboxypeptidase-A digestion of normal human hemoglobin. Hb McKees Rocks has markedly abnormal properties: its oxygen affinity is the highest of the human variants described to date; its Bohr effect is reduced; it is devoid of subunit cooperativity; and it is unaffected by 2,3-diphosphoglyceric acid. These properties are probably the consequences of decreased stability of the T quaternary conformation and are partially restored in the presence of the strong allosteric effector inositol hexaphosphate.