2g9x
From Proteopedia
| |||||||
| , resolution 2.50Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | CDK2 (Homo sapiens), CCNA2, CCNA (Bos taurus) | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of Thr 160 phosphorylated CDK2/cyclin A in complex with the inhibitor NU6271
Overview
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.
About this Structure
2G9X is a Protein complex structure of sequences from Bos taurus and Homo sapiens. Full crystallographic information is available from OCA.
Reference
Searching for cyclin-dependent kinase inhibitors using a new variant of the cope elimination., Griffin RJ, Henderson A, Curtin NJ, Echalier A, Endicott JA, Hardcastle IR, Newell DR, Noble ME, Wang LZ, Golding BT, J Am Chem Soc. 2006 May 10;128(18):6012-3. PMID:16669651
Page seeded by OCA on Thu Mar 20 17:02:09 2008
