CDK2-based CDK7 mimic as a tool for structural analysis: Biochemical validation and crystal structure with SY5609

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00603987" target="_blank" >RIV/61388963:_____/25:00603987 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15310/25:73627223
Result on the web
<a href="https://doi.org/10.1016/j.ijbiomac.2024.139117" target="_blank" >https://doi.org/10.1016/j.ijbiomac.2024.139117</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ijbiomac.2024.139117" target="_blank" >10.1016/j.ijbiomac.2024.139117</a>

Result language
angličtina
Original language name
CDK2-based CDK7 mimic as a tool for structural analysis: Biochemical validation and crystal structure with SY5609
Original language description
Cyclin-dependent kinases (CDKs) regulate cell cycle progression and transcription. CDK7 plays a pivotal role in cell division and proliferation, and the CDK7 gene often exhibits mutations or copy number loss in cancer. Pharmacological targeting of CDK7 has been proposed as a cancer treatment strategy and several inhibitors are currently in clinical trials. As opposed to CDK2, the use of structure-assisted drug design for CDK7 has been limited. We present here CDK2m7, a CDK2-based CDK7 mimic created by mutagenesis of the CDK2 active site pocket. CDK2m7 can be produced in E. coli in a fully active complex with cyclin A2 in high yield and purity. CDK2m7 exhibits a shift in inhibitor selectivity from CDK2 to CDK7 and readily crystallizes. Therefore, it can be used in structure-assisted design of CDK7 inhibitors, as demonstrated by the crystal structure of the complex with inhibitor SY5609. CDK2m7 thus represents a simple and affordable platform for CDK7 rational drug development.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology

Project
<a href="/en/project/LX22NPO5102" target="_blank" >LX22NPO5102: National institute for cancer research</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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