Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a

Nature ◽  
10.1038/26155 ◽  
1998 ◽  
Vol 395 (6699) ◽  
pp. 237-243 ◽  
Author(s):  
Alicia A. Russo ◽  
Lily Tong ◽  
Jie-Oh Lee ◽  
Philip D. Jeffrey ◽  
Nikola P. Pavletich
Keyword(s):  
Tumour Suppressor ◽  
Structural Basis ◽  
Cyclin Dependent Kinase

scholarly journals Structural basis of divergent cyclin‐dependent kinase activation by Spy1/ RINGO proteins

2017 ◽  
Vol 36 (15) ◽  
pp. 2251-2262 ◽  
Author(s):  
Denise A McGrath ◽  
Bre‐Anne Fifield ◽  
Aimee H Marceau ◽  
Sarvind Tripathi ◽  
Lisa A Porter ◽  
...  
Keyword(s):  
Structural Basis ◽  
Cyclin Dependent Kinase ◽  
Kinase Activation

Structural Basis of the Interaction of Cyclin-Dependent Kinase 2 with Roscovitine and Its Analogues Having Bioisosteric Central Heterocycles

ChemPhysChem ◽  
2017 ◽  
Vol 18 (7) ◽  
pp. 785-795 ◽  
Author(s):  
Michaela Nekardová ◽  
Ladislava Vymětalová ◽  
Prashant Khirsariya ◽  
Silvia Kováčová ◽  
Michaela Hylsová ◽  
...  
Keyword(s):  
Structural Basis ◽  
Cyclin Dependent Kinase

scholarly journals Structural basis for translational inhibition by the tumour suppressor Pdcd4

2009 ◽  
Vol 28 (3) ◽  
pp. 274-285 ◽  
Author(s):  
Portia G Loh ◽  
Hsin-Sheng Yang ◽  
Martin A Walsh ◽  
Qing Wang ◽  
Xiaoxing Wang ◽  
...  
Keyword(s):  
Tumour Suppressor ◽  
Structural Basis ◽  
Translational Inhibition

Structural basis of cyclin-dependent kinase activation by phosphorylation

1996 ◽  
Vol 3 (8) ◽  
pp. 696-700 ◽  
Author(s):  
Alicia A. Russo ◽  
Philip D. Jeffrey ◽  
Nikola P. Pavletich
Keyword(s):  
Structural Basis ◽  
Cyclin Dependent Kinase ◽  
Kinase Activation

scholarly journals Comparative Modeling of CDK9 Inhibitors to Explore Selectivity and Structure-Activity Relationships

2020 ◽  
Author(s):  
Palani Kirubakaran ◽  
George Morton ◽  
Pingfeng Zhang ◽  
Hanghang Zhang ◽  
John Gordon ◽  
...  
Keyword(s):  
Structural Changes ◽  
Comparative Modeling ◽  
Data Bank ◽  
Structural Basis ◽  
Type I ◽  
Cyclin Dependent Kinase ◽  
Active Conformation ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Promising Target

AbstractCyclin-dependent kinase 9 (CDK9) plays a key role in transcription elongation, and more recently it was also identified as the molecular target of a series of diaminothiazole compounds that reverse epigenetic silencing in a phenotypic assay. To better understand the structural basis underlying these compounds’ activity and selectivity, we developed a comparative modeling approach that we describe herein. Briefly, this approach draws upon the strong structural conservation across the active conformation of all protein kinases, and their shared pattern of interactions with Type I inhibitors. Because of this, we hypothesized that the large collection of inhibitor/kinase structures available in the Protein Data Bank (PDB) would enable accurate modeling of this diaminothiazole series in complex with each CDK family member. We apply this new comparative modeling pipeline to build each of these structural models, and then demonstrate that these models provide retrospective rationale for the structure-activity relationships that ultimately guided optimization to the lead diaminothiazole compound MC180295 (14e). We then solved the crystal structure of the 14e/CDK9 complex, and found the resulting structure to be in excellent agreement with our corresponding comparative model. Finally, inspired by these models, we demonstrate how structural changes to 14e can be used to rationally tune this compound’s selectivity profile. With the emergence of CDK9 as a promising target for therapeutic intervention in cancer, we anticipate that comparative modeling can provide a valuable tool to guide optimization of potency and selectivity of new inhibitors targeting this kinase.

Structural basis for inhibition of cyclin-dependent kinase 9 by flavopiridol

2002 ◽  
Vol 293 (1) ◽  
pp. 566-571 ◽  
Author(s):  
Walter Filgueira de Azevedo ◽  
Fernanda Canduri ◽  
Nelson José Freitas da Silveira
Keyword(s):  
Structural Basis ◽  
Cyclin Dependent Kinase

Site-Specific Phosphorylation of Lys-Ser-Pro Repeat Peptides from Neurofilament H by Cyclin-Dependent Kinase 5:  Structural Basis for Substrate Recognition

Biochemistry ◽  
1998 ◽  
Vol 37 (14) ◽  
pp. 4759-4766 ◽  
Author(s):  
Pushkar Sharma ◽  
Joseph J. Barchi, ◽  
Xiaolin Huang ◽  
Niranjana D. Amin ◽  
Howard Jaffe ◽  
...  
Keyword(s):  
Substrate Recognition ◽  
Structural Basis ◽  
Cyclin Dependent Kinase ◽  
Site Specific ◽  
Cyclin Dependent Kinase 5
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