Erlandsen H, Abola E E, Stevens R C
The Scripps Research Institute, Department of Molecular Biology, La Jolla, CA 92037, USA.
Curr Opin Struct Biol. 2000 Dec;10(6):719-30. doi: 10.1016/s0959-440x(00)00154-8.
An important goal of structural genomics is to complete the structural analysis of all the enzymes in metabolic pathways and to understand the structural similarities and differences. A preliminary glimpse of this type of analysis was achieved before structural genomics efforts with the glycolytic pathway and efforts are underway for many other pathways, including that of catecholamine metabolism. Structural enzymology necessitates a complete structural characterization, even for highly homologous proteins (greater than 80% sequence homology), as every active site has distinct structural features and it is these active site differences that distinguish one enzyme from another. Short cuts with homology modeling cannot be taken with our current knowledge base. Each enzyme structure in a pathway needs to be determined, including structures containing bound substrates, cofactors, products and transition state analogs, in order to obtain a complete structural and functional understanding of pathway-related enzymes.
结构基因组学的一个重要目标是完成代谢途径中所有酶的结构分析，并了解其结构上的异同。在结构基因组学研究之前，人们对糖酵解途径进行了此类分析的初步尝试，目前针对包括儿茶酚胺代谢途径在内的许多其他途径的研究也正在进行。结构酶学需要完整的结构表征，即使是高度同源的蛋白质（序列同源性大于80%）也不例外，因为每个活性位点都有独特的结构特征，正是这些活性位点的差异区分了一种酶与另一种酶。基于我们目前的知识库，不能采用同源建模的捷径。为了全面了解与途径相关的酶的结构和功能，需要确定途径中的每一种酶的结构，包括含有结合底物、辅因子、产物和过渡态类似物的结构。
