Briefly bound to activate: transient binding of a second catalytic magnesium activates the structure and dynamics of CDK2 kinase for catalysis.
Briefly bound to activate: transient binding of a second catalytic magnesium activates the structure and dynamics of CDK2 kinase for catalysis.
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DOI：
10.1016/j.str.2011.02.016
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发表时间：
2011-05-11
期刊：
影响因子：
5.7
通讯作者：
Young, Matthew A.
中科院分区：
文献类型：
--
作者：
Bao, Zhao Qin;Jacobsen, Douglas M.;Young, Matthew A.
我们已经确定了与ADP、底物肽和MgF 3 −结合的CDK 2/CyclinA过渡态复合物的高分辨率晶体结构。与先前的活性CDK 2结构相比，激酶的催化亚基在活性位点周围采用更封闭的构象，现在允许在活性位点中观察到第二个Mg 2+离子。结合对体外激酶活性的强[Mg 2 +]效应，结构表明第二个Mg 2+离子的瞬时结合对于实现化学反应的最大速率增强是必要的，并且Mg 2+浓度可以代表体内CDK 2活性的重要调节剂。分子动力学模拟说明了底物肽、ATP和两个Mg 2+离子的同时结合如何能够诱导活性位点的更刚性和封闭的组织，其功能是定向磷酸盐、稳定负电荷的积累并将随后活化的γ-磷酸盐与溶剂屏蔽。
We have determined high resolution crystal structures of a CDK2/CyclinA transition-state complex bound to ADP, substrate peptide and MgF3−. Compared to previous structures of active CDK2, the catalytic subunit of the kinase adopts a more closed conformation around the active site and now allows observation of a second Mg2+ ion in the active site. Coupled with a strong [Mg2+] effect on in vitro kinase activity, the structures suggest that the transient binding of the second Mg2+ ion is necessary to achieve maximum rate-enhancement of the chemical reaction and Mg2+ concentration could represent an important regulator of CDK2 activity in vivo. Molecular dynamics simulations illustrate how the simultaneous binding of substrate peptide, ATP and two Mg2+ ions is able to induce a more rigid and closed organization of the active site that functions to orient the phosphates, stabilize the buildup of negative charge, and shield the subsequently activated γ-phosphate from solvent.
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影响因子：
14.8
作者：
Liu, Y;Gray, NS
通讯作者：
Gray, NS
影响因子：
4.3
作者：
De Vivo, Marco;Cavalli, Andrea;Recanatini, Maurizio
通讯作者：
Recanatini, Maurizio
影响因子：
2.9
作者：
Bas, Delphine C.;Rogers, David M.;Jensen, Jan H.
通讯作者：
Jensen, Jan H.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
2.9
作者：
Liu, Min;Girma, Eleni;Glicksman, Marcie A.;Stein, Ross L.
通讯作者：
Stein, Ross L.