Functional Flexibility of Human Cyclin-Dependent Kinase-2 and
Its Evolutionarily Conservation

J 2008

Functional Flexibility of Human Cyclin-Dependent Kinase-2 and Its Evolutionarily Conservation

BÁRTOVÁ, Iveta, Jaroslav KOČA a Michal OTYEPKA

Základní údaje

Originální název

Functional Flexibility of Human Cyclin-Dependent Kinase-2 and Its Evolutionarily Conservation

Název česky

Flexibilita CDK2

Autoři

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

Vydání

Protein Science, COLD SPRING HARBOR LAB PRESS, 2008, 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: 3.115

Kód RIV

RIV/00216224:14310/08:00025683

Organizační jednotka

Přírodovědecká fakulta

UT WoS

000251834500004

Klíčová slova anglicky

protein; dynamics; evolutionary conservation; cell cycle; protein kinase

Štítky

cell cycle, dynamics, evolutionary conservation, PROTEIN, protein kinase

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 28. 6. 2009 19:52, prof. RNDr. Jaroslav Koča, DrSc.

Anotace

ORIG CZ

V originále

Cyclin-dependent kinase 2 (CDK2) is the most thoroughly studied of the cyclin-dependent kinases that regulate essential cellular processes, including the cell cycle, and it has become a model for studies of regulatory mechanisms at the molecular level. This contribution identifies flexible and rigid regions of CDK2 based on temperature B-factors acquired from both X-ray data and molecular dynamics simulations. In addition, the biological relevance of the identified flexible regions and their motions is explored using information from the essential dynamics analysis related to conformational changes of CDK2 and knowledge of its biological function(s). The conserved regions of CMGC protein kinases primary sequences are located in the most rigid regions identified in our analyses, with the sole exception of the absolutely conserved G13 in the tip of the glycine-rich loop. The conserved rigid regions are important for nucleotide binding, catalysis, and substrate recognition. In contrast, the most flexible regions correlate with those where large conformational changes occur during CDK2 regulation processes. The rigid regions flank and form a rigid skeleton for the flexible regions, which appear to provide the plasticity required for CDK2 regulation. Unlike the rigid regions (which as mentioned are highly conserved) no evidence of evolutionary conservation was found for the flexible regions.

Česky

Flexibilita CDK2

Návaznosti

LC06030, projekt VaV

Název: Biomolekulární centrum

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

MSM0021622413, záměr

Název: Proteiny v metabolismu a při interakci organismů s prostředím

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Proteiny v metabolismu a při interakci organismů s prostředím

Citovat

BÁRTOVÁ, Iveta, Jaroslav KOČA a Michal OTYEPKA. Functional Flexibility of Human Cyclin-Dependent Kinase-2 and Its Evolutionarily Conservation. Protein Science. COLD SPRING HARBOR LAB PRESS, 2008, roč. 17, č. 1, s. 22-33. ISSN 0961-8368.

@article{747372,
   author = {Bártová, Iveta and Koča, Jaroslav and Otyepka, Michal},
   article_number = {1},
   keywords = {protein; dynamics; evolutionary conservation; cell cycle; protein kinase},
   language = {eng},
   issn = {0961-8368},
   journal = {Protein Science},
   title = {Functional Flexibility of Human Cyclin-Dependent Kinase-2 and Its Evolutionarily Conservation},
   volume = {17},
   year = {2008}
}

TY  - JOUR
ID  - 747372
AU  - Bártová, Iveta - Koča, Jaroslav - Otyepka, Michal
PY  - 2008
TI  - Functional Flexibility of Human Cyclin-Dependent Kinase-2 and Its Evolutionarily Conservation
JF  - Protein Science
VL  - 17
IS  - 1
SP  - 22-33
EP  - 22-33
PB  - COLD SPRING HARBOR LAB PRESS
SN  - 09618368
KW  - protein
KW  - dynamics
KW  - evolutionary conservation
KW  - cell cycle
KW  - protein kinase
N2  - Cyclin-dependent kinase 2 (CDK2) is the most thoroughly studied of the cyclin-dependent kinases that regulate essential cellular processes, including the cell cycle, and it has become a model for studies of regulatory mechanisms at the molecular level. This contribution identifies flexible and rigid regions of CDK2 based on temperature B-factors acquired from both X-ray data and molecular dynamics simulations. In addition, the biological relevance of the identified flexible regions and their motions is explored using information from the essential dynamics analysis related to conformational changes of CDK2 and knowledge of its biological function(s). The conserved regions of CMGC protein kinases primary sequences are located in the most rigid regions identified in our analyses, with the sole exception of the absolutely conserved G13 in the tip of the glycine-rich loop. The conserved rigid regions are important for nucleotide binding, catalysis, and substrate recognition. In contrast, the most flexible regions correlate with those where large conformational changes occur during CDK2 regulation processes. The rigid regions flank and form a rigid skeleton for the flexible regions, which appear to provide the plasticity required for CDK2 regulation. Unlike the rigid regions (which as mentioned are highly conserved) no evidence of evolutionary conservation was found for the flexible regions.
ER  -

BÁRTOVÁ, Iveta, Jaroslav KOČA a Michal OTYEPKA. Functional Flexibility of Human Cyclin-Dependent Kinase-2 and Its Evolutionarily Conservation. \textit{Protein Science}. COLD SPRING HARBOR LAB PRESS, 2008, roč.~17, č.~1, s.~22-33. ISSN~0961-8368.

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