Structure of the pseudokinase VRK3 reveals a degraded catalytic site, a highly conserved kinase fold, and a putative regulatory binding site.
Structure of the pseudokinase VRK3 reveals a degraded catalytic site, a highly conserved kinase fold, and a putative regulatory binding site.
复制标题
DOI：
10.1016/j.str.2008.10.018
复制
发表时间：
2009-01-14
期刊：
影响因子：
--
通讯作者：
Manning G
中科院分区：
文献类型：
--
作者：
Scheeff ED;Eswaran J;Bunkoczi G;Knapp S;Manning G
大约10%的蛋白激酶被预测为酶失活的假激酶，但激酶失活的结构细节仍不清楚。我们提出了假激酶VRK3的第一个结构，以及它最接近的活性亲戚VRK2的结构。活性位点区域的深刻变化是催化活性丧失的基础，并且由于结合口袋中的残基取代，VRK3不能结合ATP。然而，VRK3仍然与VRK2具有惊人的结构相似性，并且似乎被锁定在假活性构象中。VRK3还保留了在缺乏酶功能的情况下令人惊讶的残基相互作用；它们似乎扮演着VRK3剩余功能所需的重要架构角色。值得注意的是，VRK3具有“倒置”的序列保守模式：尽管活性位点保守性差，但部分分子表面显示出非常高的保守性，这表明它们形成了解释VRK3进化保留的关键相互作用。
About 10% of all protein kinases are predicted to be enzymatically inactive pseudokinases, but the structural details of kinase inactivation have remained unclear. We present the first structure of a pseudokinase, VRK3, and that of its closest active relative, VRK2. Profound changes to the active site region underlie the loss of catalytic activity, and VRK3 cannot bind ATP because of residue substitutions in the binding pocket. However, VRK3 still shares striking structural similarity with VRK2, and appears to be locked in a pseudoactive conformation. VRK3 also conserves residue interactions that are surprising in the absence of enzymatic function; these appear to play important architectural roles required for the residual functions of VRK3. Remarkably, VRK3 has an “inverted” pattern of sequence conservation: although the active site is poorly conserved, portions of the molecular surface show very high conservation, suggesting that they form key interactions that explain the evolutionary retention of VRK3.
登录
查看更多内容
影响因子：
14.9
作者：
Benson DA;Cavanaugh M;Clark K;Karsch-Mizrachi I;Lipman DJ;Ostell J;Sayers EW
通讯作者：
Sayers EW
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
2.9
作者：
Grant, BD;Hemmer, W;Taylor, SS
通讯作者：
Taylor, SS
影响因子：
5.3
作者：
Kang, Tae-Hong;Park, Do-Young;Kim, Kyong-Tai
通讯作者：
Kim, Kyong-Tai
影响因子：
14.9
作者：
Davis IW;Leaver-Fay A;Chen VB;Block JN;Kapral GJ;Wang X;Murray LW;Arendall WB 3rd;Snoeyink J;Richardson JS;Richardson DC
通讯作者：
Richardson DC