An experimental approach to mapping the binding surfaces of crystalline proteins
An experimental approach to mapping the binding surfaces of crystalline proteins
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DOI：
10.1021/jp952516o
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发表时间：
1996-02-15
影响因子：
--
通讯作者：
Ringe, D
中科院分区：
文献类型：
--
作者：
Allen, KN;Bellamacina, CR;Ringe, D
猪胰腺弹性蛋白酶已被用作模型酶的设计和开发的晶体学方法，允许映射的结合表面的蛋白质，通过解决其晶体结构在各种有机溶剂。这种方法的最终目标是帮助药物设计过程，其中每个选定的有机分子代表较大抑制剂分子中的给定官能团。这种多溶剂晶体结构（MSCS）的方法在多拷贝同时搜索（MCSS）的方法中具有理论对应物（Miranker，A.; Karplus，M.蛋白质：结构，功能，Genet. 1991，11，29-34），是第一个实验方法，可以用来作为一个检查的理论。本文介绍了以乙腈为探针有机溶剂的MSCS方法。与水溶液中的结构相比，所涉及的程序不会引起弹性蛋白酶结构的显著变化，并且将在活性位点中发现的乙腈分子的位置与属于与弹性蛋白酶结合的已知抑制剂的类似官能团的位置进行比较。
Porcine pancreatic elastase has been used as the model enzyme in the design and development of a crystallographic method that allows mapping of the binding surface of a protein by solving its crystal structure in a variety of organic solvents. The ultimate goal of this method is to aid in the process of drug design, where each of the chosen organic molecules represents a given functional group in a larger inhibitor molecule. This method of multiple solvent crystal structures (MSCS) has a theoretical counterpart in the method of multiply copy simultaneous search (MCSS) (Miranker, A.; Karplus, M. Proteins: Struct., Funct., Genet. 1991, 11, 29-34) and is the first experimental method that can be used as a check to the theory. The MSCS method is presented here with acetonitrile as the probe organic solvent. The procedure involved does not cause significant changes in the structure of elastase as compared to the structure in aqueous solution, and the positions found for the acetonitrile molecules in the active site are compared to those of similar functional groups belonging to known inhibitors bound to elastase.