Crystal structures of the catalytic domain of human protein kinase associated with apoptosis and tumor suppression
Crystal structures of the catalytic domain of human protein kinase associated with apoptosis and tumor suppression
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DOI：
10.1038/nsb1001-899
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发表时间：
2001-10-01
期刊：
影响因子：
--
通讯作者：
Egli, M
中科院分区：
文献类型：
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作者：
Tereshko, V;Teplova, T;Egli, M
我们以高达1.5埃的分辨率确定了死亡相关蛋白激酶（DAPK）的x射线晶体结构，这是一个新的促凋亡和肿瘤抑制丝氨酸/苏氨酸激酶家族的第一个被描述的成员。在载子形式、与不可水解的AMPPnP配合物以及由激酶、AMPPnP和Mg2+或Mn2+组成的三元配合物中，研究了活性位点的几何形状。这些结构揭示了先前未描述的水介导的蛋白质激酶中保存的赖氨酸与ATP的β -和γ -磷酸之间相互作用的稳定性，以及离子结合时活性位点的构象变化。将这些结构与其他几种激酶的核苷酸三磷酸复合物进行比较，揭示了DAPK催化结构域的许多独特特征，其中n端结构域中有一个高度有序的碱性环，可能参与酶的调节。
We have determined X-ray crystal structures with up to 1.5 Angstrom resolution of the catalytic domain of death-associated protein kinase (DAPK), the first described member of a novel family of pro-apoptotic and tumor-suppressive serine/threonine kinases. The geometry of the active site was studied in the apo form, in a complex with nonhydrolyzable AMPPnP and in a ternary complex consisting of kinase, AMPPnP and either Mg2+ or Mn2+. The structures revealed a previously undescribed water-mediated stabilization of the interaction between the lysine that is conserved in protein kinases and the beta- and gamma -phosphates of ATP, as well as conformational changes at the active site upon ion binding. Comparison between these structures and nucleotide triphosphate complexes of several other kinases disclosed a number of unique features of the DAPK catalytic domain, among which is a highly ordered basic loop in the N-terminal domain that may participate in enzyme regulation.