9ESV

CDK2-cyclin A in complex with FragLite 19

Summary for 9ESV

• Entry DOI: 10.2210/pdb9esv/pdb
• Descriptor: Cyclin-dependent kinase 2, Cyclin-A2, 4-bromo-2-methoxyphenol, ... (4 entities in total)
• Functional Keywords: cyclin-dependent kinase, fraglite, cdk2, cyclin a, fragment, cell cycle
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 132171.78

Authors

Hope, I.,Martin, M.P.,Waring, M.J.,Noble, M.E.M.,Endicott, J.A.,Tatum, N.J. (deposition date: 2024-03-26, release date: 2025-09-03)

Primary citation

Hope, I.,Martin, M.P.,Jiang, Z.,Waring, M.J.,Noble, M.E.M.,Endicott, J.A.,Tatum, N.J.
Crystallographic fragment screening of CDK2-cyclin A: FragLites map sites of protein-protein interaction.
Structure, 2025

PubMed Abstract: Sites of protein-protein interaction (PPI) are potentially more selective binding sites for therapeutics than protein substrate-binding sites. PPIs include distinct regions frequently called "hotspots," sites of key amino acid interactions. Prospective identification of these hotspots through X-ray crystallographic screening could assist in the identification of separation of function mutants for experimental validation, enhance confidence in AI-generated multiprotein complex predictions, and accelerate development of selective chemical probes. To explore these applications, we utilize the FragLite library to examine the binding surfaces of CDK2-cyclin A. The many protein- and peptide-CDK2-cyclin A complexes that have been structurally characterized make this complex an appropriate test case. We show that FragLites comprehensively map both known sites of protein-protein interaction on CDK2-cyclin A and identify a possible uncharacterized site, providing a structural method toward directing mechanistic studies and starting points for chemical probe design.

PubMed: 40816275
DOI: 10.1016/j.str.2025.07.016

Experimental method

X-RAY DIFFRACTION (2.397 Å)