2G9X

Structure of Thr 160 phosphorylated CDK2/cyclin A in complex with the inhibitor NU6271

Summary for 2G9X

• Entry DOI: 10.2210/pdb2g9x/pdb
• Descriptor: Cell division protein kinase 2, Cyclin-A2, 3-({2-[(4-{[6-(CYCLOHEXYLMETHOXY)-9H-PURIN-2-YL]AMINO}PHENYL)SULFONYL]ETHYL}AMINO)PROPAN-1-OL, ... (4 entities in total)
• Functional Keywords: transferase, serine/threonine protein kinase, atp-binding, cell cycle, phosphorylation, transferase-cell cycle complex, transferase/cell cycle
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P30274
• Total number of polymer chains: 4
• Total formula weight: 129269.56

Authors

Echalier, A.,Endicott, J.A.,Noble, M.E. (deposition date: 2006-03-07, release date: 2006-05-23, Last modification date: 2024-11-20)

Primary citation

Griffin, R.J.,Henderson, A.,Curtin, N.J.,Echalier, A.,Endicott, J.A.,Hardcastle, I.R.,Newell, D.R.,Noble, M.E.,Wang, L.Z.,Golding, B.T.
Searching for Cyclin-Dependent Kinase Inhibitors Using a New Variant of the Cope Elimination.
J.Am.Chem.Soc., 128:6012-6013, 2006

PubMed Abstract: beta-Piperidinoethylsulfides are oxidized by m-chloroperbenzoic acid to intermediates containing both N-oxide and sulfone functions. These undergo a Cope-type elimination to a vinylsulfone that can be captured by amines to afford beta-aminoethylsulfones. When a beta-aminoethylsulfone group is linked to the 4-position of a phenyl group attached at N-2 of O6-cyclohexylmethylguanine, the resulting derivatives are inhibitors of the cyclin-dependent kinase CDK2. One of the most potent inhibitors (IC50 = 45 nM) contained a N-3-hydroxypropyl group on the aminoethylsulfonyl substituent. The crystal structure of this inhibitor bound to CDK2/cyclin A was determined and shows an unusual network of hydrogen bonds. The synthetic methodology developed can be utilized in multiple-parallel format and has numerous potential applications in medicinal chemistry.

PubMed: 16669651
DOI: 10.1021/ja060595j

Experimental method

X-RAY DIFFRACTION (2.5 Å)