| BÁRTOVÁ, Iveta, Michal OTYEPKA, Zdeněk KŘÍŽ a Jaroslav KOČA. The Mechanism of Inhibition of the Cyclin-Dependent Kinase-2 as Revealed by the Molecular Dynamics Study on the Complex CDK2 with the Peptide Substrate HHASPRK. Online. Protein Science. COLD SPRING HARBOR LAB PRESS, 2005, roč. 14, č. 2, s. 445-451. ISSN 0961-8368. [citováno 2024-04-23] |
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@article{567646,
author = {Bártová, Iveta and Otyepka, Michal and Kříž, Zdeněk and Koča, Jaroslav},
article_number = {2},
keywords = {cell cycle; CDK inhibition; phosphorylated tyrosine and threonine; glycine?rich loop; GxGxxG motif},
language = {eng},
issn = {0961-8368},
journal = {Protein Science},
title = {The Mechanism of Inhibition of the Cyclin-Dependent Kinase-2 as Revealed by the Molecular Dynamics Study on the Complex CDK2 with the Peptide Substrate HHASPRK},
volume = {14},
year = {2005}
}
TY - JOUR
ID - 567646
AU - Bártová, Iveta - Otyepka, Michal - Kříž, Zdeněk - Koča, Jaroslav
PY - 2005
TI - The Mechanism of Inhibition of the Cyclin-Dependent Kinase-2 as Revealed by the Molecular Dynamics Study on the Complex CDK2 with the Peptide Substrate HHASPRK
JF - Protein Science
VL - 14
IS - 2
SP - 445-451
EP - 445-451
PB - COLD SPRING HARBOR LAB PRESS
SN - 09618368
KW - cell cycle
KW - CDK inhibition
KW - phosphorylated tyrosine and threonine
KW - glycine?rich loop
KW - GxGxxG motif
N2 - Molecular dynamics (MD) simulations were used to explain structural details of cyclin-dependent kinase-2 (CDK2) inhibition by phosphorylation at T14 and/or Y15 located in the glycine-rich loop (G-loop). Tennanosecond- long simulations of fully active CDK2 in a complex with a short peptide (HHASPRK) substrate and of CDK2 inhibited by phosphorylation of T14 and/or Y15 were produced. The inhibitory phosphorylations at T14 and/or Y15 show namely an ATP misalignment and a G-loop shift (5 Å) causing the opening of the substrate binding box. The biological functions of the G-loop and GxGxxG motif evolutionary conservation in protein kinases are discussed. The position of the ATP -phosphate relative to the phosphorylation site (S/T) of the peptide substrate in the active CDK2 is described and compared with inhibited forms of CDK2. The MD results clearly provide an explanation previously not known as to why a basic residue (R/K) is preferred at the P2 position in phosphorylated S/T peptide substrates.
ER -
BÁRTOVÁ, Iveta, Michal OTYEPKA, Zdeněk KŘÍŽ a Jaroslav KOČA. The Mechanism of Inhibition of the Cyclin-Dependent Kinase-2 as Revealed by the Molecular Dynamics Study on the Complex CDK2 with the Peptide Substrate HHASPRK. Online. \textit{Protein Science}. COLD SPRING HARBOR LAB PRESS, 2005, roč.~14, č.~2, s.~445-451. ISSN~0961-8368. [citováno 2024-04-23]
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