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. Protein Science. COLD SPRING HARBOR LAB PRESS, 2005, roč. 14, č. 2, s. 445-451. ISSN 0961-8368. |
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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. \textit{Protein Science}. COLD SPRING HARBOR LAB PRESS, 2005, roč.~14, č.~2, s.~445-451. ISSN~0961-8368.
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