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CDK1 structures reveal conserved and unique features of the essential cell cycle CDK

Nature communications, 2015-04, Vol.6 (1), p.6769-6769, Article 6769 [Peer Reviewed Journal]

Copyright Nature Publishing Group Apr 2015 ;Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2015 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. ;ISSN: 2041-1723 ;EISSN: 2041-1723 ;DOI: 10.1038/ncomms7769 ;PMID: 25864384

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Title:
CDK1 structures reveal conserved and unique features of the essential cell cycle CDK
Author: Brown, Nicholas R ; Korolchuk, Svitlana ; Martin, Mathew P ; Stanley, Will A ; Moukhametzianov, Rouslan ; Noble, Martin E M ; Endicott, Jane A
Subjects: Adenosine Triphosphate - chemistry ; Animals ; Binding, Competitive ; Cancer ; Carrier Proteins - chemistry ; Carrier Proteins - genetics ; Cattle ; CDC2 Protein Kinase ; CDC2-CDC28 Kinases - chemistry ; CDC2-CDC28 Kinases - genetics ; Cell cycle ; Cell Cycle Proteins - chemistry ; Cell Cycle Proteins - genetics ; Conserved Sequence ; Crystal structure ; Crystallography, X-Ray ; Cyclin A ; Cyclin A - chemistry ; Cyclin A - genetics ; Cyclin B ; Cyclin B - chemistry ; Cyclin B - genetics ; Cyclin-dependent kinase ; Cyclin-dependent kinase 2 ; Cyclin-Dependent Kinase 2 - chemistry ; Cyclin-Dependent Kinase 2 - genetics ; Cyclin-Dependent Kinases - antagonists & inhibitors ; Cyclin-Dependent Kinases - chemistry ; Cyclin-Dependent Kinases - genetics ; Dephosphorylation ; Eukaryotes ; Gene Expression ; Humans ; Kinetics ; Models, Molecular ; Nature conservation ; Peptides - chemical synthesis ; Peptides - chemistry ; Protein Binding ; Protein Kinase Inhibitors - chemistry ; Protein Stability ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Recombinant Fusion Proteins - chemistry ; Recombinant Fusion Proteins - genetics ; Substrate Specificity ; Substrates ; Thermal stability
Is Part Of: Nature communications, 2015-04, Vol.6 (1), p.6769-6769, Article 6769
Description: CDK1 is the only essential cell cycle CDK in human cells and is required for successful completion of M-phase. It is the founding member of the CDK family and is conserved across all eukaryotes. Here we report the crystal structures of complexes of CDK1-Cks1 and CDK1-cyclin B-Cks2. These structures confirm the conserved nature of the inactive monomeric CDK fold and its ability to be remodelled by cyclin binding. Relative to CDK2-cyclin A, CDK1-cyclin B is less thermally stable, has a smaller interfacial surface, is more susceptible to activation segment dephosphorylation and shows differences in the substrate sequence features that determine activity. Both CDK1 and CDK2 are potential cancer targets for which selective compounds are required. We also describe the first structure of CDK1 bound to a potent ATP-competitive inhibitor and identify aspects of CDK1 structure and plasticity that might be exploited to develop CDK1-selective inhibitors.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 2041-1723
EISSN: 2041-1723
DOI: 10.1038/ncomms7769
PMID: 25864384
Source: MEDLINE
PubMed Central
ProQuest Central
DOAJ Directory of Open Access Journals

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CDK1 structures reveal conserved and unique features of the essential cell cycle CDK

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