β141 Leu is not deleted in the unstable haemoglobin Atlanta‐Coventry but is replaced by a novel amino acid of mass 129 daltons
β141 Leu is not deleted in the unstable haemoglobin Atlanta‐Coventry but is replaced by a novel amino acid of mass 129 daltons
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不稳定的血红蛋白亚特兰大-考文垂中的 β141 Leu 并未被删除，而是被质量为 129 道尔顿的新型氨基酸取代
DOI：
10.1111/j.1365-2141.1992.tb08179.x
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发表时间：
1992
影响因子：
6.5
通讯作者：
P. George
中科院分区：
文献类型：
--
作者：
S. Brennan;John E. Shaw;J. Allen;P. George
对亚特兰大-考文垂血红蛋白β链结构的重新研究（β75 Leu→Pro，β141 Leu缺失）证实存在两种异常;然而，通过液体二次离子质谱法对异常β Co 14胰蛋白酶肽的分析表明，β141 Leu（质量113道尔顿）未缺失，而是被质量129道尔顿的新氨基酸取代。肽β Co 14中的新氨基酸在pH6.5时不带电荷，比亮氨酸更亲脂，易被胰凝乳蛋白酶和羧肽酶A裂解。我们认为新的残基可能是羟亮氨酸，并且它是由于E螺旋（E19）中β75 Leu→Pro突变引起的血红素环境扰动而导致β141 Leu翻译后氧化的结果。这一提议与最近的DNA分析完全一致，该分析表明βAt‐Co不是第三个β珠蛋白基因的产物，并且两个β珠蛋白基因都不是。βA或βAtlanta，含有β141 Leu密码子的缺失。随后，我们在另外两种不稳定血红蛋白的β141位发现了这种修饰的氨基酸，这两种血红蛋白都涉及E螺旋血红素侧的突变。
Reinvestigation of the structure of the β‐chain of Hb Atlanta‐Coventry (β75 Leu→Pro, β141 Leu deleted) confirmed the presence of two abnormalities; however, analysis of the aberrant βCo14 tryptic peptide by liquid secondary ion mass spectrometry indicated that the β141 Leu (mass 113 daltons) was not deleted but replaced by a novel amino acid of mass 129 daltons. The new amino acid in peptide βCo14 was uncharged at pH 6·5, more hydrophillic than leucine and susceptible to cleavage by both chymotrypsin and carboxypeptidase A. We propose that the new residue is likely to be hydroxyleucine and that it results from post‐translational oxidation of β141 Leu as a consequence of perturbation of the haem environment caused by the β75 Leu→Pro mutation in the E helix (E19). This proposal is entirely consistent with recent DNA analysis which showed that βAt‐Co was not the product of a third β‐globin gene and that neither of the two β‐globin genes. βA nor βAtlanta, contained a deletion of the β141 Leu codon. We have subsequently found this modified amino acid at position β141 in two other unstable haemoglobins, both of which involve mutations on the haem side of the E helix.