Evolution of Structure and Function in the Carbonic Anhydrase Isozymes of Mammals
Evolution of Structure and Function in the Carbonic Anhydrase Isozymes of Mammals
复制标题
哺乳动物碳酸酐酶同工酶的结构和功能的进化
DOI：
10.1007/978-3-642-67572-0_18
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发表时间：
1980
影响因子：
2.2
通讯作者：
Ya
中科院分区：
文献类型：
--
作者：
R. Tashian;D. Hewett‐Emmett;S. K. Stroup;M. Goodman;Ya
对来自许多种的碳酸酐酶同工酶（命名为CA I和CA II）的一级结构的比较研究表明，这些同工酶中同源位置上的近一半（46%）的氨基酸残基保持不变（参见图1）。Tashian，1977）。由于两种碳酸酐酶同工酶之间的这种高度序列同源性以及人CA I和CA II的三维结构非常相似的事实（Kannan等人，1975; Liljas等人，1972; Notstrand等人，1974），很明显，这些同工酶的结构基因来自相同的祖先基因。已知这些同工酶在它们对热和变性试剂的稳定性、比活性以及环磺酰胺、卤化物和阴离子的抑制方面存在差异，有时是显著的（参见第13页）。Lindskog等人，1971; Maren，1976; Tashian，1977）。因此，一些关键的变化必须在结构（活性位点残基？）以解释观察到的功能差异（Notstrand等，1974; Kannan等人，1977年）。最近，已经报道了来自哺乳动物骨骼肌的碳酸酐酶的第三种同工酶，我们将其命名为CA III（Holmes，1977; Koester等人，1977; Tashian，1977，1978; Tashian等人，1978年）的一些性质显着不同的CA I和II。例如，CA III同工酶的CO2水合酶和酯酶活性以及磺酰胺结合亲和力远低于CA I和II同工酶，尤其是酯酶活性和磺酰胺结合亲和力（Holmes，1977; Koester et al.，1977; Tashian等人，1978; Carter等人，1979年）。此外，CA III的构象性质似乎与CA I和CA II有独特的不同（Koester和Noltmann，1979）。
Comparative studies on the primary structures of the carbonic anhydrase isozymes, designated CA I and CA II, from a number of mammlian species have shown that nearly one half (46%) of the amino acid residues at homologous positions in these isozymes has remained invariant (cf. Tashian, 1977). Because of this high degree of sequence homology between the two carbonic anhydrase isozymes and the fact that the three-dimensional structures of human CA I and CA II are very similar (Kannan et al., 1975; Liljas et al., 1972; Notstrand et al., 1974), it is clear that the structural genes for these isozymes arose from the same ancestral gene. These isozymes are known to differ, sometimes markedly, in their stabilities to heat and denaturing reagents, specific activities, and inhibition by cyclic sulfonamides, halides, and anions (Cf. Lindskog et al., 1971; Maren, 1976; Tashian, 1977). Thus, some critical changes must have evolved in the structures (active site residues?) of these isozymes to account for the observed functional differences (Notstrand et al., 1974; Kannan et al., 1977). Recently, a third isozyme of carbonic anhydrase has been reported, which we have designated CA III, from mammalian skeletal muscle (Holmes, 1977; Koester et al., 1977; Tashian, 1977, 1978; Tashian et al., 1978) some of whose properties differ strikingly from those of CA I and II. For example, the CO2 hydratase and esterase activities and sulfonamide binding affinity of the CA III isozymes are much lower than those of the CA I and II isozymes, especially the esterase activity and sulfonamide binding affinity (Holmes, 1977; Koester et al., 1977; Tashian et al., 1978; Carter et al., 1979). In addition, the conformational properties of CA III appear to be uniquely different from CA I and CA II (Koester and Noltmann, 1979).