OTYEPKA, Michal, Iveta BÁRTOVÁ, Zdeněk KŘÍŽ and Jaroslav KOČA. DIFFERENT MECHANISMS OF CDK5 AND CDK2 ACTIVATION AS REVEALED BY CDK5/P25 AND CDK2/CYCLIN A DYNAMICS. The Journal of biological chemistry. 2006, vol. 281, No 11, p. 7271-7281. ISSN 0021-9258.
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Basic information
Original name DIFFERENT MECHANISMS OF CDK5 AND CDK2 ACTIVATION AS REVEALED BY CDK5/P25 AND CDK2/CYCLIN A DYNAMICS
Name in Czech Rozdílný mechanismus CDK5 a CDK2 activace. Dynamika komplexů CDK5/p25 a CDK2/Cyklin A
Authors OTYEPKA, Michal (203 Czech Republic), Iveta BÁRTOVÁ (203 Czech Republic), Zdeněk KŘÍŽ (203 Czech Republic) and Jaroslav KOČA (203 Czech Republic, guarantor).
Edition The Journal of biological chemistry, 2006, 0021-9258.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10403 Physical chemistry
Country of publisher Czech Republic
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 5.808
RIV identification code RIV/00216224:14310/06:00015728
Organization unit Faculty of Science
UT WoS 000236030900045
Keywords in English cell cycle; CDK5 regulation; CDK2 regulation; glycine?rich loop; CDK dynamics
Tags CDK dynamics, CDK2 regulation, CDK5 regulation, cell cycle, glycine?rich loop
Tags International impact, Reviewed
Changed by Changed by: Mgr. Iveta Bártová, Ph.D., učo 15185. Changed: 5/1/2008 21:56.
Abstract
A detailed analysis is presented of the dynamics of human CDK5 in complexes with the protein activator p25 and the purine-like inhibitor roscovitine. These, and other findings related to the activation of CDK5 are critically reviewed from a molecular perspective. In addition, the results obtained on the behavior of CDK5 are compared to data on CDK2 to assess the differences and similarities between the two kinases in terms of (i) roscovitine binding, (ii) regulatory subunit association, (iii) conformational changes in the T-loop following CDK/regulatory subunit complex formation and (iv) specificity in CDK/regulatory subunit recognition. An energy decomposition analysis, used for these purposes, revealed why the binding of p25 alone is sufficient to stabilize the extended active T-loop conformation of CDK5, whereas the equivalent conformational change in CDK2 requires both the binding of Cyclin A and phosphorylation of the Thr160 residue. The interaction energy of the CDK5 T-loop with p25 is about 26 kcal.mol-1 greater than that of the CDK2 T-loop with Cyclin A. The binding pattern between CDK5 and p25 was compared to that of CDK2/Cyclin A to find specific regions involved in CDK/regulatory subunit recognition. The analyses performed revealed that the aNT-helix of Cyclin A interacts with the a6-a7 loop and the a7 helix of CDK2, but these regions do not interact in the CDK5/p25 complex. Further differences between the CDK5/p25 and CDK2/Cyclin A systems studied are discussed with respect to their specific functionality.
Abstract (in Czech)
Aktivace a Inhibice CDK5 a CDK2
Links
GD204/03/H016, research and development projectName: Strukturní biofyzika makromolekul
Investor: Czech Science Foundation, Structural biophysics of macromolecules
MSM0021622413, plan (intention)Name: Proteiny v metabolismu a při interakci organismů s prostředím
Investor: Ministry of Education, Youth and Sports of the CR, Proteins in metabolism and interaction of organisms with the environment
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