Activation and Inhibition of Cyclin-Dependent Kinase-2 by
Phosphorylation; A Molecular Dynamics Study Reveals the
Functional Importance of the Glycine-Rich Loop

J 2004

Activation and Inhibition of Cyclin-Dependent Kinase-2 by Phosphorylation; A Molecular Dynamics Study Reveals the Functional Importance of the Glycine-Rich Loop

BÁRTOVÁ, Iveta, Michal OTYEPKA, Zdeněk KŘÍŽ a Jaroslav KOČA

Základní údaje

Originální název

Activation and Inhibition of Cyclin-Dependent Kinase-2 by Phosphorylation; A Molecular Dynamics Study Reveals the Functional Importance of the Glycine-Rich Loop

Název česky

Aktivace a Inhibice CDK2

Autoři

BÁRTOVÁ, Iveta (203 Česká republika, garant), Michal OTYEPKA (203 Česká republika), Zdeněk KŘÍŽ (203 Česká republika) a Jaroslav KOČA (203 Česká republika)

Vydání

Protein Science, COLD SPRING HARBOR LAB PRESS, 2004, 0961-8368

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10403 Physical chemistry

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 4.116

Kód RIV

RIV/00216224:14310/04:00010530

Organizační jednotka

Přírodovědecká fakulta

UT WoS

000221630900002

Klíčová slova anglicky

cell cycle; CDK regulation; phosphorylated tyrosine; threonine

Štítky

CDK regulation, cell cycle, phosphorylated tyrosine, threonine

Změněno: 31. 5. 2005 12:17, Mgr. Iveta Bártová, Ph.D.

Anotace

ORIG CZ

V originále

Nanoseconds long molecular dynamics (MD) trajectories of differently active complexes of human cyclin-dependent kinase 2 (inactive CDK2/ATP, semi-active CDK2/Cyclin A/ATP, fully-active pT160-CDK2/Cyclin A/ATP, inhibited pT14-; pY15-; and pT14,pY15,pT160-CDK2/Cyclin A/ATP) are compared. The MD simulations results of CDK2 inhibition by phosphorylation at T14 and/or Y15 sites provide insight into structural aspects of CDK2 deactivation. The inhibitory sites are localized in the glycine-rich loop (G-loop) positioned opposite the activation T-loop. Phosphorylation of T14 and both inhibitory sites T14 and Y15 together causes ATP misalignment for phosphorylation and G-loop conformational change. This conformational change leads to the opening of the CDK2 substrate binding box. The phosphorylated Y15 residue negatively affects substrate binding or its correct alignment for ATP terminal phospho-group transfer to the CDK2 substrate. The MD simulations of the CDK2 activation process provide results in agreement with previous X-ray data.

Česky

Aktivace a Inhibice CDK2

Návaznosti

GV201/98/K041, projekt VaV

Název: HCILAB - Laboratoř interakcí člověka s počítačem

Investor: Grantová agentura ČR, HCILAB - Laboratoř interakcí člověka s počítačem

LN00A016, projekt VaV

Název: BIOMOLEKULÁRNÍ CENTRUM

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Biomolekulární centrum

MSM 143100005, záměr

Název: Strukturně-funkční vztahy biomolekul a jejich role v metabolismu

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Strukturně-funkční vztahy biomolekul a jejich role v metabolismu

Citovat

BÁRTOVÁ, Iveta, Michal OTYEPKA, Zdeněk KŘÍŽ a Jaroslav KOČA. Activation and Inhibition of Cyclin-Dependent Kinase-2 by Phosphorylation; A Molecular Dynamics Study Reveals the Functional Importance of the Glycine-Rich Loop. Protein Science. COLD SPRING HARBOR LAB PRESS, 2004, roč. 13, č. 6, s. 1449-1457. ISSN 0961-8368.

@article{561317,
   author = {Bártová, Iveta and Otyepka, Michal and Kříž, Zdeněk and Koča, Jaroslav},
   article_number = {6},
   keywords = {cell cycle; CDK regulation; phosphorylated tyrosine; threonine},
   language = {eng},
   issn = {0961-8368},
   journal = {Protein Science},
   title = {Activation and Inhibition of Cyclin-Dependent Kinase-2 by Phosphorylation; A Molecular Dynamics Study Reveals the Functional Importance of the Glycine-Rich Loop},
   volume = {13},
   year = {2004}
}

TY  - JOUR
ID  - 561317
AU  - Bártová, Iveta - Otyepka, Michal - Kříž, Zdeněk - Koča, Jaroslav
PY  - 2004
TI  - Activation and Inhibition of Cyclin-Dependent Kinase-2 by Phosphorylation; A Molecular Dynamics Study Reveals the Functional Importance of the Glycine-Rich Loop
JF  - Protein Science
VL  - 13
IS  - 6
SP  - 1449-1457
EP  - 1449-1457
PB  - COLD SPRING HARBOR LAB PRESS
SN  - 09618368
KW  - cell cycle
KW  - CDK regulation
KW  - phosphorylated tyrosine
KW  - threonine
N2  - Nanoseconds long molecular dynamics (MD) trajectories of differently active complexes of human cyclin-dependent kinase 2 (inactive CDK2/ATP, semi-active CDK2/Cyclin A/ATP, fully-active pT160-CDK2/Cyclin A/ATP, inhibited pT14-; pY15-; and pT14,pY15,pT160-CDK2/Cyclin A/ATP) are compared. The MD simulations results of CDK2 inhibition by phosphorylation at T14 and/or Y15 sites provide insight into structural aspects of CDK2 deactivation. The inhibitory sites are localized in the glycine-rich loop (G-loop) positioned opposite the activation T-loop. Phosphorylation of T14 and both inhibitory sites T14 and Y15 together causes ATP misalignment for phosphorylation and G-loop conformational change. This conformational change leads to the opening of the CDK2 substrate binding box. The phosphorylated Y15 residue negatively affects substrate binding or its correct alignment for ATP terminal phospho-group transfer to the CDK2 substrate. The MD simulations of the CDK2 activation process provide results in agreement with previous X-ray data.
ER  -

BÁRTOVÁ, Iveta, Michal OTYEPKA, Zdeněk KŘÍŽ a Jaroslav KOČA. Activation and Inhibition of Cyclin-Dependent Kinase-2 by Phosphorylation; A Molecular Dynamics Study Reveals the Functional Importance of the Glycine-Rich Loop. \textit{Protein Science}. COLD SPRING HARBOR LAB PRESS, 2004, roč.~13, č.~6, s.~1449-1457. ISSN~0961-8368.

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