Access of ligands to cavities within the core of a protein is rapid
Access of ligands to cavities within the core of a protein is rapid
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DOI：
10.1038/nsb0696-516
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发表时间：
1996-06-01
期刊：
影响因子：
--
通讯作者：
Dahlquist, FW
中科院分区：
文献类型：
--
作者：
Feher, VA;Baldwin, EP;Dahlquist, FW
我们已经调查了幅度和时间尺度内的核心的蛋白质使用吲哚和苯结合到工程疏水腔T4溶菌酶的交换动力学的波动。变体-苯配合物的晶体结构表明，这些配体进入cove需要骨架原子的相对大的尺度波动（1-2埃）。尽管如此，这些配体进入空腔迅速，双分子速率常数类似于10（6）-10（7）M（-1）s（-1）和低活化势垒，2-5 kcal mol（-1）。这些结果表明，蛋白质核心在毫秒到微秒的时间尺度上经历了实质性的波动，小分子进入蛋白质内部并不受空间位阻的强烈限制。
We have investigated the magnitude and timescale of fluctuations within the core of a protein using the exchange kinetics of indole and benzene binding to engineered hydrophobic cavities in T4 lysozyme. The crystal structures of variant-benzene complexes suggest that relatively large scale fluctuations (1-2 Angstrom) of backbone atoms are required for entry of these ligands into the cove. Nonetheless, these ligands enter the cavities rapidly, with bimolecular rate constants of similar to 10(6)-10(7) M(-1) s(-1) and a low activation barrier, 2-5 kcal mol(-1) These results suggest that protein cores undergo substantial fluctuations on the millisecond to microsecond timescale and that entry of small molecules into protein interiors is not strongly limited by steric occlusion.