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@inproceedings{587742, author = {Otyepka, Michal and Bártová, Iveta and Kříž, Zdeněk and Koča, Jaroslav}, address = {Wroclaw}, booktitle = {Cellular and Molecular Biology Letters}, keywords = {Molecular Dynamics; Interaction Energy; phosphorylation; CDK2; CDK5}, language = {eng}, location = {Wroclaw}, isbn = {1425-8153}, pages = {116-117}, publisher = {Department of Genetic Biochemistry, Institute of Biochemistry, University of Wroclaw}, title = {Dynamics of human CDK2 and CDK5 studied by computer simulations}, year = {2005} }
TY - JOUR ID - 587742 AU - Otyepka, Michal - Bártová, Iveta - Kříž, Zdeněk - Koča, Jaroslav PY - 2005 TI - Dynamics of human CDK2 and CDK5 studied by computer simulations PB - Department of Genetic Biochemistry, Institute of Biochemistry, University of Wroclaw CY - Wroclaw SN - 14258153 KW - Molecular Dynamics KW - Interaction Energy KW - phosphorylation KW - CDK2 KW - CDK5 N2 - Cyclin-dependent kinases (CDKs) control progression of the cell cycle, apoptosis, transcription, and differentiation in neuronal cells. CDK consists of two subunits, a catalytic subunit kinase and regulatory protein cyclin. Several CDKs (CDK1, CDK2, CDK4 and CDK6) show a dual mechanism of activation based on cyclin binding and phosphorylation of the activation loop. This model of activation, however, does not apply to CDK5, despite 60% sequence identity to CDK2. CDK5 is a unique member of the CDK family, as it is not activated by a cyclin. Instead, CDK5 activity is triggered by p35 and p39, proteins whose expression is limited to neurons and to a few other cell types [1]. Association of CDK5 with p35 or p39 is enough to full activate CDK5. Furthermore, CDK5 seems not to be activated by phosphorylation in the activation loop, even if this contains a potential phosphorylation site (Ser159, equivalent to Thr160 of CDK2) [2, 3]. Additionally, phosphorylation of the glycine-rich loop (G-loop) is inhibitory for CDK2 or CDK1 but it seems to be stimulatory for CDK5 [4]. The phosphorylation of Thr14 and Tyr15 in the G-loop is an important element of CDK regulation machinery. Structural aspects of that were recently studied on CDK2 using molecular dynamics [6, 7]. The Tyr15-CDK5 activatory phosphorylation structural mechanism has been speculated by Mapelli et al. [3] namely in context of roscovitine binding. The simulation on phosho-Tyr15-CDK5/p25/roscovitine complex shows that Tyr15 phosphorylation leads to Tyr15 exposure to solvent and also to G-loop shift. Phoshorylated Tyr15 behaves similarly to phospho-Tyr15 in CDK2, which causes also exposure of phosphate group to the solvent but produces also notable shift of the G-loop [7]. The analysis of interaction energies between roscovitine and CDK5 and pTyr15-CDK5 documents that Tyr15 phosphorylation has negligible influence on roscovitine binding in according to experimental observations [3]. Also, the interaction pattern between CDK/regulatory unit will be discussed in detail (specifita CDK-Cyklin). ER -
OTYEPKA, Michal, Iveta BÁRTOVÁ, Zdeněk KŘÍŽ a Jaroslav KOČA. Dynamics of human CDK2 and CDK5 studied by computer simulations. In \textit{Cellular and Molecular Biology Letters}. Wroclaw: Department of Genetic Biochemistry, Institute of Biochemistry, University of Wroclaw, 2005, s.~116-117. ISBN~1425-8153.
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