Site-directed mutagenesis of the glycine-rich loop of death associated protein kinase (DAPK) identifies it as a key structure for catalytic activity.
Site-directed mutagenesis of the glycine-rich loop of death associated protein kinase (DAPK) identifies it as a key structure for catalytic activity.
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对富含甘氨酸的死亡环相关蛋白激酶 (DAPK) 进行定点诱变，将其确定为催化活性的关键结构。
DOI：
10.1016/j.bbamcr.2010.11.011
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Grum-Tokars,Valerie
中科院分区：
文献类型：
--
作者：
McNamara,LaurieK;Brunzelle,JosephS;Schavocky,JamesP;Watterson,DMartin;Grum-Tokars,Valerie
Death associated protein kinase (DAPK) is a calmodulin (CaM)-regulated protein kinase that is a therapeutic target for central nervous system (CNS) disorders. We report here the results of studies that test the hypothesis of McNamara et al. (2009) that conformational selection in DAPK's glycine-rich region is key for catalytic activity. The hypothesis was tested by site-directed mutagenesis of glutamine-23 (Q23) in the middle of this loop. The glycine-rich loop exhibits localized differences in structure among DAPK conformations that correlate with different stages of the catalytic cycle. Changing the Q23 to a Valine (V23), found at the corresponding position in another CaM regulated protein kinase, results in a reduced catalytic efficiency. High resolution X-ray crystal structures of various conformations of the Q23V mutant DAPK and their superimposition with the corresponding conformations from wild type catalytic domain reveal localized changes in the glycine-rich region. The effect of the mutation on DAPK catalytic activity and the finding of only localized changes in the DAPK structure provide experimental evidence implicating conformational selection in this domain with activity. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
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影响因子：
4.8
作者：
Hemmer, W;McGlone, M;Taylor, SS
通讯作者：
Taylor, SS
DOI：
10.1016/s1570-9639(02)00453-3
发表时间：
2002-11
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
A. Schumacher;A. Velentza;D. Watterson;Mark S. Wainwright
通讯作者：
A. Schumacher;A. Velentza;D. Watterson;Mark S. Wainwright
DOI：
10.1038/nsb1001-899
发表时间：
2001-10-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Tereshko, V;Teplova, T;Egli, M
通讯作者：
Egli, M
3 – 钙调蛋白调节的蛋白激酶
DOI：
10.1016/b978-0-08-092636-0.50007-4
发表时间：
1998
期刊：
--
影响因子：
--
作者：
T. Lukas;S. Mirzoeva;D. Watterson
通讯作者：
D. Watterson
影响因子：
3.5
作者：
Li, Yonghong;Grupe, Andrew;Goate, Alison
通讯作者：
Goate, Alison