Toggle Main Menu Toggle Search

Open Access padlockePrints

Mutational analysis supports a structural model for the cell cycle protein kinase p34

Lookup NU author(s): Professor Jane Endicott

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

Structural models for the eukaryotic cell cycle control protein p34 from human, S.pombe and S.cerevisiae have been derived from the crystallographic coordinates of the cAMP-dependent protein kinase (cAPK) catalytic subunit (active conformation) and compared with the structure of inactive CDK2 apoenzyme. Differences between the p34 and cAPK catalytic sites provide a possible explanation for their different substrate specificities. The p34 models localize Tyr15 and Thr14 close to the sites of catalysis and substrate recognition where their phosphorylation could inhibit p34 kinase activity either by blocking MgATP or substrate binding. The conserved sequences PSTAIRE and LYLIFEFL are both close to the catalytic site and accessible on the protein surface available to mediate interactions with other proteins. It is predicted that p34 has an active-site cleft composed almost entirely of sequences common to all protein kinases and sequences unique to the p34 protein family. Genetic and biochemical analyses of p34 have shown that it interacts extensively with a number of other proteins. The model allows the relative disposition of these sites of mutation to each other and to the sites of catalysis and substrate recognition to be appreciated. Surface regions on p34 that are important for function have been identified. These sites identify residues that may interact with p13(suc1), cyclin, p107(wee1) and p80(cdc25).


Publication metadata

Author(s): Endicott JA, Nurse P, Johnson LN

Publication type: Article

Publication status: Published

Journal: Protein Engineering

Year: 1994

Volume: 7

Issue: 2

Pages: 243-253

Print publication date: 01/02/1994

ISSN (print): 0269-2139

ISSN (electronic): 1741-0134

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/protein/7.2.243

DOI: 10.1093/protein/7.2.243


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share