Structure-based analysis of catalysis and substrate definition in the HIT protein family
Structure-based analysis of catalysis and substrate definition in the HIT protein family
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DOI：
10.1126/science.278.5336.286
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发表时间：
1997-10-10
期刊：
影响因子：
56.9
通讯作者：
Hendrickson, WA
中科院分区：
文献类型：
--
作者：
Lima, CD;Klein, MG;Hendrickson, WA
组氨酸三联体（hitidine triad， HIT）蛋白家族是自然界中最普遍和高度保守的蛋白家族之一，但HIT家族的任何成员的生物活性尚未被确定。利用脆弱组氨酸三联体蛋白（FHIT）和蛋白激酶C相互作用蛋白（PKCI），以结构为基础的方法来阐明体内配体和反应的特征。这两种酶的类人酶、底物类似物、五价过渡态类似物和产物板的晶体结构揭示了催化机制，并定义了催化所需的底物特征，从而将HIT家族统一为核苷酸水解酶、转移酶或两者兼有。本文描述的方法可能有助于鉴定通过基因组学鉴定的蛋白质家族之间的结构-功能关系。
The histidine triad (HIT) protein family is among the most ubiquitous and highly conserved in nature, but a biological activity has not yet been identified for any member of the HIT family. Fragile histidine triad protein (FHIT) and protein kinase C interacting protein (PKCI) were used in a structure-based approach to elucidate characteristics of in vivo ligands and reactions. Crystallographic structures of ape, substrate analog, pentacovalent transition-state analog, and product slates of both enzymes reveal a catalytic mechanism and define substrate characteristics required for catalysis, thus unifying the HIT family as nucleotidyl hydrolases, transferases, or both. The approach described here may be useful in identifying structure-function relations between protein families identified through genomics.