2005
Dynamics of human CDK2 and CDK5 studied by computer simulations
OTYEPKA, Michal, Iveta BÁRTOVÁ, Zdeněk KŘÍŽ a Jaroslav KOČAZákladní údaje
Originální název
Dynamics of human CDK2 and CDK5 studied by computer simulations
Název česky
Studioum dynamiky CDK2 a CDK5 pomoci pocitacovych simulaci
Autoři
OTYEPKA, Michal (203 Česká republika), Iveta BÁRTOVÁ (203 Česká republika, garant), Zdeněk KŘÍŽ (203 Česká republika) a Jaroslav KOČA (203 Česká republika)
Vydání
Wroclaw, Cellular and Molecular Biology Letters, od s. 116-117, 2 s. 2005
Nakladatel
Department of Genetic Biochemistry, Institute of Biochemistry, University of Wroclaw
Další údaje
Jazyk
angličtina
Typ výsledku
Stať ve sborníku
Obor
10403 Physical chemistry
Stát vydavatele
Česká republika
Utajení
není předmětem státního či obchodního tajemství
Organizační jednotka
Přírodovědecká fakulta
ISBN
1425-8153
Klíčová slova anglicky
Molecular Dynamics; Interaction Energy; phosphorylation; CDK2; CDK5
Štítky
Změněno: 25. 9. 2006 14:19, Mgr. Zdeněk Kříž, Ph.D.
V originále
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).
Česky
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).
Návaznosti
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