Další formáty:
BibTeX
LaTeX
RIS
@inproceedings{491005,
author = {Bártová, Iveta and Otyepka, Michal and Kříž, Zdeněk and Koča, Jaroslav},
address = {Praha},
booktitle = {Book of Abstracts},
edition = {2003},
keywords = {molekular dynamics; CDK regulation; cell cycle},
language = {eng},
location = {Praha},
pages = {8-8},
publisher = {Workshop on Modeling Interactions in Biomolecules},
title = {COMPUTER SIMULATIONS OF CYCLIN-DEPENDENT KINASE-2 NOTES ABOUT INHIBITION},
year = {2003}
}
TY - JOUR
ID - 491005
AU - Bártová, Iveta - Otyepka, Michal - Kříž, Zdeněk - Koča, Jaroslav
PY - 2003
TI - COMPUTER SIMULATIONS OF CYCLIN-DEPENDENT KINASE-2 NOTES ABOUT INHIBITION
PB - Workshop on Modeling Interactions in Biomolecules
CY - Praha
KW - molekular dynamics
KW - CDK regulation
KW - cell cycle
N2 - Cyclin-dependent kinases (CDKs) are enzymes controlling the eukaryotic cell cycle. Cell-cycle dependent oscillations in CDK activity are induced by complex mechanisms that include binding to positive regulatory subunits and phosphorylation at positive and negative regulatory sites. Binding to Cyclin A or Cyclin E is required for CDK2 activation. CDK2 obtains full activity by phosphorylation of the T160 residue in the activation segment (T-loop) and it is inhibited by phosphorylation on inhibitory sites at Y15 and/or T14 in the Glycine rich loop (G-loop). CDK2 is inhibited also by interactions with various native protein inhibitors. The primary function of CDK is to catalyze the phosphoryl transfer of the ATP g-phosphate to serine or threonine hydroxyl in the protein target substrate. The adenosine triphosphate is native substrate of CDK2. Human CDK2 contains the classical bi-lobal kinase fold. The ATP binding site is located in the deep cleft between two lobes. The N-terminal domain is composed mainly of b-sheet, containing five anti-parallel b-strands, and one helix (the C-helix). The larger C-terminal domain is predominantly a-helical. This study compares behavior of inactive, semi-, fully-active CDK2, and CDK2 inhibited by phosphorylation at T14, T14/Y15, and Y15 residues. The molecular dynamics simulations with the Cornell et al. force field as implemented in the AMBER software package were utilized. Starting structures for MD simulations were obtained from the Brookhaven protein data bank (www.pdb.org) with PDB access codes 1HCK, 1FIN, and 1JST for inactive, semi-, and fully-active CDK2, respectively. Inhibited complexes of CDK2 were prepared by phosphorylation of the fully active CDK2 on the inhibitory sites. Activation of CDK2 by phosphorylation involves various conformational changes, including the reorientation of the ATP phosphate moiety and key residues involved in the ATP phospho-transfer stabilization. Inhibition of CDK2 by phosphorylation involves also reorientation of the ATP phosphate moiety and further reconformation of the ATP and the protein substrate binding site. Results of conformational behavior of the ATP, T-loop, Glycine rich loop (G-loop), and other key residues will be presented.
ER -
BÁRTOVÁ, Iveta, Michal OTYEPKA, Zdeněk KŘÍŽ a Jaroslav KOČA. COMPUTER SIMULATIONS OF CYCLIN-DEPENDENT KINASE-2 NOTES ABOUT INHIBITION. In \textit{Book of Abstracts}. 2003. vyd. Praha: Workshop on Modeling Interactions in Biomolecules, 2003, s.~8.
|
