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CDK2-based CDK7 mimic as a tool for structural analysis: Biochemical validation and crystal structure with SY5609
International Journal of Biological Macromolecules 294: 139117 (2025)
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.
Chiroptical spectroscopy complemented by quantum chemical calculations accurately predicts the absolute configuration of P-chirogenic compounds
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 330: 125674 (2025)
Simultaneous treatment with palm-LEAP2(1–14) and feeding high-fat diet attenuates liver lipid metabolism but not obesity: Sign of selective resistance to palm-LEAP2(1–14)
Molecular and Cellular Endocrinology 597: 112442 (2025)
SPR is a fast and straightforward method to estimate the binding constants of cyclic dinucleotides to their binding partners, such as STING or poxin
Biophysical Chemistry 2025: Early View