Structural prediction of the interaction of the tumor suppressor p27ass="a-plus-plus">KIP1 with cyclin A/CDK2 identifies a novel catalytically relevant determinant
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- 作者：Jinyu Li ; Jörg Vervoorts ; Paolo Carloni ; Giulia Rossetti…
- 关键词：Cyclin ; dependent kinase ; Tumor suppressor ; Molecular modeling ; p27KIP1 ; Phosphorylation
- 刊名：BMC Bioinformatics
- 出版年：2017
- 出版时间：December 2017
- 年：2017
- 卷：18
- 期：1
- 全文大小：2066KB
- 刊物主题：Bioinformatics; Microarrays; Computational Biology/Bioinformatics; Computer Appl. in Life Sciences; Algorithms;
- 出版者：BioMed Central
- ISSN：1471-2105
- 卷排序：18
文摘
BackgroundThe cyclin-dependent kinase 2 (CDK2) together with its cyclin E and A partners is a central regulator of cell growth and division. Deregulation of CDK2 activity is associated with diseases such as cancer. The analysis of substrates identified S/T-P-X-R/K/H as the CDK2 consensus sequence. The crystal structure of cyclin A/CDK2 with a short model peptide supports this sequence and identifies key interactions. However, CDKs use additional determinants to recognize substrates, including the RXL motif that is read by the cyclin subunits. We were interested to determine whether additional amino acids beyond the minimal consensus sequence of the well-studied substrate and tumor suppressor p27KIP1 were relevant for catalysis.