CONVERGENCE OF ACTIVE-CENTER GEOMETRIES
CONVERGENCE OF ACTIVE-CENTER GEOMETRIES
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DOI：
10.1021/bi00642a019
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发表时间：
1977-01-01
期刊：
影响因子：
2.9
通讯作者：
EVENTOFF, W
中科院分区：
文献类型：
--
作者：
GARAVITO, RM;ROSSMANN, MG;EVENTOFF, W
比较了乳酸脱氢酶和3-磷酸甘油醛脱氢酶、胰凝乳蛋白酶和木瓜蛋白酶以及3-磷酸甘油醛脱氢酶和木瓜蛋白酶的活性中心几何形状。在脱氢酶中，烟酰胺环围绕糖苷键的方向由底物立体化学决定。羧酰胺部分的正确定位使得烟酰胺上的 C4 原子和底物的活性碳能够紧密接近。一旦相对于酶中的官能团建立了底物或底物中间体的构象，烟酰胺环的A侧或B侧特异性就被预先确定。如果催化结构域的蛋白质折叠是保守的，则从共同前体不同进化而来的脱氢酶必须保持烟酰胺特异性。发现胰凝乳蛋白酶和木瓜蛋白酶酰化过程中产生的四面体中间体具有相反的手性，而木瓜蛋白酶和3-磷酸甘油醛脱氢酶的酰化过程中产生的四面体中间体可被认为是同一手性。因此，丝氨酸蛋白酶、枯草杆菌蛋白酶和胰凝乳蛋白酶家族的蛋白酶属于一方面，而半胱氨酸酶、3-磷酸甘油醛脱氢酶和木瓜蛋白酶属于另一方面。
Comparisons were made between the active center geometries of lactate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase, chymotrypsin and papain and glyceraldehyde-3-phosphate dehydrogenase and papain. In the dehydrogenases, orientation of the nicotinamide ring about the glycosidic bond is determined by the substrate stereochemistry. The proper positioning of the carboxyamide moiety allows for the close approach of the C4 atom on the nicotinamide and the reactive carbon of the substrate. Once the conformation of the substrate or substrate intermediate was established with respect to the functional groups in the enzyme, the A- or B-side specificity of the nicotinamide ring is predetermined. Dehydrogenases which are divergently evolving from a common precursor must maintain the nicotinamide specificity if the protein fold of the catalytic domain is conserved. The tetrahedral intermediates produced during acylation of chymotrypsin and papain are found to be of opposite hand, while those of papain and glyceraldehyde-3-phosphate dehydrogenase can be regarded to be of the same hand. Thus the serine proteases, subtilisin and those of the chymotrypsin family, are of one hand while the cysteine enzymes, glyceraldehyde-3-phosphate dehydrogenase and papain, are of the other.