9ET2

CDK2-cyclin A in complex with FragLite 11

9ET2 の概要

• エントリーDOI: 10.2210/pdb9et2/pdb
• 分子名称: Cyclin-dependent kinase 2, Cyclin-A2, ~{N}-(4-bromophenyl)ethanamide, ... (4 entities in total)
• 機能のキーワード: cyclin-dependent kinase, fraglite, cdk2, cyclin a, fragment, cell cycle
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 131200.72

構造登録者

Hope, I.,Martin, M.P.,Waring, M.J.,Noble, M.E.M.,Endicott, J.A.,Tatum, N.J. (登録日: 2024-03-26, 公開日: 2025-04-09, 最終更新日: 2025-11-19)

主引用文献

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, 33:1971-, 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

実験手法

X-RAY DIFFRACTION (2.37 Å)