DIFFERENT MECHANISMS OF CDK5 AND CDK2 ACTIVATION AS REVEALED BY
CDK5/P25 AND CDK2/CYCLIN A DYNAMICS

J 2006

DIFFERENT MECHANISMS OF CDK5 AND CDK2 ACTIVATION AS REVEALED BY CDK5/P25 AND CDK2/CYCLIN A DYNAMICS

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

Základní údaje

Originální název

DIFFERENT MECHANISMS OF CDK5 AND CDK2 ACTIVATION AS REVEALED BY CDK5/P25 AND CDK2/CYCLIN A DYNAMICS

Název česky

Rozdílný mechanismus CDK5 a CDK2 activace. Dynamika komplexů CDK5/p25 a CDK2/Cyklin A

Autoři

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

Vydání

The Journal of biological chemistry, 2006, 0021-9258

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: 5.808

Kód RIV

RIV/00216224:14310/06:00015728

Organizační jednotka

Přírodovědecká fakulta

UT WoS

000236030900045

Klíčová slova anglicky

cell cycle; CDK5 regulation; CDK2 regulation; glycine?rich loop; CDK dynamics

Štítky

CDK dynamics, CDK2 regulation, CDK5 regulation, cell cycle, glycine?rich loop

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 1. 2008 21:56, Mgr. Iveta Bártová, Ph.D.

Anotace

ORIG CZ

V originále

A detailed analysis is presented of the dynamics of human CDK5 in complexes with the protein activator p25 and the purine-like inhibitor roscovitine. These, and other findings related to the activation of CDK5 are critically reviewed from a molecular perspective. In addition, the results obtained on the behavior of CDK5 are compared to data on CDK2 to assess the differences and similarities between the two kinases in terms of (i) roscovitine binding, (ii) regulatory subunit association, (iii) conformational changes in the T-loop following CDK/regulatory subunit complex formation and (iv) specificity in CDK/regulatory subunit recognition. An energy decomposition analysis, used for these purposes, revealed why the binding of p25 alone is sufficient to stabilize the extended active T-loop conformation of CDK5, whereas the equivalent conformational change in CDK2 requires both the binding of Cyclin A and phosphorylation of the Thr160 residue. The interaction energy of the CDK5 T-loop with p25 is about 26 kcal.mol-1 greater than that of the CDK2 T-loop with Cyclin A. The binding pattern between CDK5 and p25 was compared to that of CDK2/Cyclin A to find specific regions involved in CDK/regulatory subunit recognition. The analyses performed revealed that the aNT-helix of Cyclin A interacts with the a6-a7 loop and the a7 helix of CDK2, but these regions do not interact in the CDK5/p25 complex. Further differences between the CDK5/p25 and CDK2/Cyclin A systems studied are discussed with respect to their specific functionality.

Česky

Aktivace a Inhibice CDK5 a CDK2

Návaznosti

GD204/03/H016, projekt VaV

Název: Strukturní biofyzika makromolekul

Investor: Grantová agentura ČR, Strukturní biofyzika makromolekul

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

OTYEPKA, Michal, Iveta BÁRTOVÁ, Zdeněk KŘÍŽ a Jaroslav KOČA. DIFFERENT MECHANISMS OF CDK5 AND CDK2 ACTIVATION AS REVEALED BY CDK5/P25 AND CDK2/CYCLIN A DYNAMICS. The Journal of biological chemistry. 2006, roč. 281, č. 11, s. 7271-7281. ISSN 0021-9258.

@article{637685,
   author = {Otyepka, Michal and Bártová, Iveta and Kříž, Zdeněk and Koča, Jaroslav},
   article_number = {11},
   keywords = {cell cycle; CDK5 regulation; CDK2 regulation; glycine?rich loop; CDK dynamics},
   language = {eng},
   issn = {0021-9258},
   journal = {The Journal of biological chemistry},
   title = {DIFFERENT MECHANISMS OF CDK5 AND CDK2 ACTIVATION AS REVEALED BY CDK5/P25 AND CDK2/CYCLIN A DYNAMICS},
   volume = {281},
   year = {2006}
}

TY  - JOUR
ID  - 637685
AU  - Otyepka, Michal - Bártová, Iveta - Kříž, Zdeněk - Koča, Jaroslav
PY  - 2006
TI  - DIFFERENT MECHANISMS OF CDK5 AND CDK2 ACTIVATION AS REVEALED BY CDK5/P25 AND CDK2/CYCLIN A DYNAMICS
JF  - The Journal of biological chemistry
VL  - 281
IS  - 11
SP  - 7271-7281
EP  - 7271-7281
SN  - 00219258
KW  - cell cycle
KW  - CDK5 regulation
KW  - CDK2 regulation
KW  - glycine?rich loop
KW  - CDK dynamics
N2  - A detailed analysis is presented of the dynamics of human CDK5 in complexes with the protein activator p25 and the purine-like inhibitor roscovitine. These, and other findings related to the activation of CDK5 are critically reviewed from a molecular perspective. In addition, the results obtained on the behavior of CDK5 are compared to data on CDK2 to assess the differences and similarities between the two kinases in terms of (i) roscovitine binding, (ii) regulatory subunit association, (iii) conformational changes in the T-loop following CDK/regulatory subunit complex formation and (iv) specificity in CDK/regulatory subunit recognition. An energy decomposition analysis, used for these purposes, revealed why the binding of p25 alone is sufficient to stabilize the extended active T-loop conformation of CDK5, whereas the equivalent conformational change in CDK2 requires both the binding of Cyclin A and phosphorylation of the Thr160 residue. The interaction energy of the CDK5 T-loop with p25 is about 26 kcal.mol-1 greater than that of the CDK2 T-loop with Cyclin A. The binding pattern between CDK5 and p25 was compared to that of CDK2/Cyclin A to find specific regions involved in CDK/regulatory subunit recognition. The analyses performed revealed that the aNT-helix of Cyclin A interacts with the a6-a7 loop and the a7 helix of CDK2, but these regions do not interact in the CDK5/p25 complex. Further differences between the CDK5/p25 and CDK2/Cyclin A systems studied are discussed with respect to their specific functionality.
ER  -

OTYEPKA, Michal, Iveta BÁRTOVÁ, Zdeněk KŘÍŽ a Jaroslav KOČA. DIFFERENT MECHANISMS OF CDK5 AND CDK2 ACTIVATION AS REVEALED BY CDK5/P25 AND CDK2/CYCLIN A DYNAMICS. \textit{The Journal of biological chemistry}. 2006, roč.~281, č.~11, s.~7271-7281. ISSN~0021-9258.

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