Detailed Information on Publication Record
2004
A Molecular Dynamics Study of the Cyclin-Dependent Kinase-2 (CDK2) with Substrate Peptide (HHASPRK), Inhibition of CDK2 by Phosphorylation
BÁRTOVÁ, Iveta, Michal OTYEPKA, Zdeněk KŘÍŽ and Jaroslav KOČABasic information
Original name
A Molecular Dynamics Study of the Cyclin-Dependent Kinase-2 (CDK2) with Substrate Peptide (HHASPRK), Inhibition of CDK2 by Phosphorylation
Name (in English)
A Molecular Dynamics Study of the Cyclin-Dependent Kinase-2 (CDK2) with Substrate Peptide (HHASPRK), Inhibition of CDK2 by Phosphorylation
Authors
BÁRTOVÁ, Iveta (203 Czech Republic, guarantor), Michal OTYEPKA (203 Czech Republic), Zdeněk KŘÍŽ (203 Czech Republic) and Jaroslav KOČA (203 Czech Republic)
Edition
Praha, Materials in Structure Chemistry, Biology, Physics and Technology, p. 42-43, 2 pp. 2004
Publisher
Krystalografická společnost
Other information
Language
Czech
Type of outcome
Stať ve sborníku
Field of Study
10403 Physical chemistry
Country of publisher
Czech Republic
Confidentiality degree
není předmětem státního či obchodního tajemství
References:
RIV identification code
RIV/00216224:14310/04:00009964
Organization unit
Faculty of Science
ISBN
1211 - 5894
Keywords in English
Cyclin dependent kinase; inhibition; phosphorylation; molecular dynamics
Změněno: 21/3/2004 15:10, Mgr. Zdeněk Kříž, Ph.D.
V originále
The cyclin-dependent kinase, CDK2, regulates the eukaryotic cell cycle at the G1; S boundary. CDKs activity is regulated by complex mechanism including binding to positive regulatory subunit and phosphorylation at positive and/or negative regulatory sites [1]. For activation CDK2 requires binding to Cyclin A or Cyclin E. The CDK2 obtains full activity after phosphorylation of the threonine residue (T160) in the activation segment (T-loop) [2]. CDK2 catalyzes the phosphoryl transfer of the adenosine-5-triphosphate (ATP) g-phosphate to serine or threonine hydroxyl in the protein substrate. The CDKs activity is inhibited in several ways, for example, by (de)phosphorylation, interaction with various natural protein inhibitors [3,4], etc. The CDK2 can be negatively regulated by phosphorylation at Y15 and, to a lesser extent, at T14 in the glycine-rich loop (G-loop) [5]. This work describes behavior of the fully active CDK2 (pT160-CDK2/Cyclin A/ATP complex) with substrate peptide (HHASPRK) and CDK2 inhibited by phosphorylation at T14, Y15, and T14/Y15 residues altogether in the G-loop using molecular dynamics simulations with the Cornell et al. force field as implemented in the AMBER software package [6]. Inhibited complexes of CDK2 were prepared from pT160-CDK2/Cyclin A/HHASPRK/ATP (1QMZ PDB ID code) by phosphorylation of the T14 and/or Y15 residues. Enzyme dynamics was studied during 8 ns long trajectory. Differences in conformational behavior of key residues for substrate binding and phosphoryl transfer of fully active vs. inhibited CDK2 will be presented.
In English
The cyclin-dependent kinase, CDK2, regulates the eukaryotic cell cycle at the G1; S boundary. CDKs activity is regulated by complex mechanism including binding to positive regulatory subunit and phosphorylation at positive and/or negative regulatory sites [1]. For activation CDK2 requires binding to Cyclin A or Cyclin E. The CDK2 obtains full activity after phosphorylation of the threonine residue (T160) in the activation segment (T-loop) [2]. CDK2 catalyzes the phosphoryl transfer of the adenosine-5-triphosphate (ATP) g-phosphate to serine or threonine hydroxyl in the protein substrate. The CDKs activity is inhibited in several ways, for example, by (de)phosphorylation, interaction with various natural protein inhibitors [3,4], etc. The CDK2 can be negatively regulated by phosphorylation at Y15 and, to a lesser extent, at T14 in the glycine-rich loop (G-loop) [5]. This work describes behavior of the fully active CDK2 (pT160-CDK2/Cyclin A/ATP complex) with substrate peptide (HHASPRK) and CDK2 inhibited by phosphorylation at T14, Y15, and T14/Y15 residues altogether in the G-loop using molecular dynamics simulations with the Cornell et al. force field as implemented in the AMBER software package [6]. Inhibited complexes of CDK2 were prepared from pT160-CDK2/Cyclin A/HHASPRK/ATP (1QMZ PDB ID code) by phosphorylation of the T14 and/or Y15 residues. Enzyme dynamics was studied during 8 ns long trajectory. Differences in conformational behavior of key residues for substrate binding and phosphoryl transfer of fully active vs. inhibited CDK2 will be presented.
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