Nonspecific medium effects versus specific group positioning in the antibody and albumin catalysis of the base-promoted ring-opening reactions of benzisoxazoles
Nonspecific medium effects versus specific group positioning in the antibody and albumin catalysis of the base-promoted ring-opening reactions of benzisoxazoles
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DOI：
10.1021/ja0490727
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发表时间：
2004-07-07
影响因子：
15
通讯作者：
Hilvert, D
中科院分区：
文献类型：
--
作者：
Hu, YF;Houk, KN;Hilvert, D
溶剂、抗体和白蛋白影响苯并异恶唑的碱催化反应速率的机制已经在理论上进行了探索。取代基的影响和反应速率在几种溶剂中，在抗体中，并在白蛋白的新的实验数据报告。对水和乙腈中的反应进行了量子力学计算，并完成了过渡态与抗体34 E4的同源模型和人血清白蛋白的X射线结构的对接。由相对非极性基团包围的催化极性基团（抗体34E4中的谷氨酸和人血清白蛋白中的赖氨酸）组成的微环境存在于两种催化蛋白中。
The mechanisms by which solvents, antibodies, and albumins influence the rates of base-catalyzed reactions of benzisoxazoles have been explored theoretically. New experimental data on substituent effects and rates of reactions in several solvents, in an antibody, and in an albumin are reported. Quantum mechanical calculations were carried out for the reactions in water and acetonitrile, and docking of the transition state into a homology model of antibody 34E4 and an X-ray structure of human serum albumin was accomplished. A microenvironment made up of catalytic polar groups (glutamate in antibody 34E4 and lysine in human serum albumin) surrounded by relatively nonpolar groups is present in both catalytic proteins.