Stereochemistry of carbon monoxide binding to normal human adult and Cowtown haemoglobins.
Stereochemistry of carbon monoxide binding to normal human adult and Cowtown haemoglobins.
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一氧化碳与正常成人和牛城血红蛋白结合的立体化学。
DOI：
10.1016/0022-2836(90)90262-k
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发表时间：
1990
影响因子：
5.6
通讯作者：
Reynaud,JP
中科院分区：
文献类型：
--
作者：
Derewenda,Z;Dodson,G;Emsley,P;Harris,D;Nagai,K;Perutz,M;Renaud,JP;Reynaud,JP
一碳一氧血红蛋白A和Cowtown（His 146 J？+）的结构Leu）分别在2.2 A（1 A=@1 nm）和2.3 A分辨率下进行了精细化。F 'e-GO线的最小二乘拟合与血红素法线形成约6”的角度。Fe-CO基团从线性弯曲约7”。CO配体血红蛋白中的卟啉是褶皱的。血红素的这种变形和Fe-GO基团的扭曲可以解释血红蛋白的低CO亲和力。C-末端残基的电子密度较低，但足以清楚地区分组氨酰和亮氨酰残基。除了1468之外，这两种结构之间的相似性意味着碱性玻尔效应的减弱仅仅是由于组氨酸被亮氨酸取代。合成卟啉在氧和一氧化碳之间的分配系数为几千。在人类血红蛋白中，这一数值减少到约250。这种还原对生命是必不可少的，因为一氧化碳是在红细胞溶解后卟啉分解时内源性产生的。血红素口袋被定制为容纳氧，其与铁的键被弯曲到血红素法线，但不容纳CO，其平行于血红素法线结合，除非受到空间位阻的干扰。问题是远端残基的空间位阻是否将血红蛋白的CO亲和力降低到生理可耐受的水平。
The structures of carbonmonoxyhaemoglobins A and Cowtown (Hisl46J?+ Leu) have been refined at 2.2 A (1 A=@ 1 nm) and 2.3 A resolution, respectively. The least squares fit to the F’e-GO line makes an angle to the haem normal of about 6”. The Fe-CO group is bent from linearity by about 7”. The porphyrins in the CO liganded haemoglobins are ruffled. This deformation of the haem and the distortion of the Fe-GO group may explain the low CO affinity of haemoglobin. The electron density for the C-terminal residues is low but sufficient to distinguish the histidyl and leucyl residues clearly. The similarity between these two structures, apart from 1468, means that the reduced alkaline Bohr effect is due solely to the replacement of histidine by a leucine.Synthetic porphyrins have partition coefficients between oxygen and carbonmonoxide of the order of a few thousand. In human haemoglobin this is reduced to about 250. This reduction is essential for life, since carbonmonoxide is produced endogenously in the breakdown of porphyrin that follows the lysis of red blood cells. The haem pocket is tailored to accommodate oxygen whose bond with iron is bent to the haem normal, but not CO, which binds parallel to the haem normal unless perturbed by steric hindrance. The question is whether steric hindrance by the distal residues lowers the CO affinity of haemoglobin to a physiological tolerable level.