2g9x
From Proteopedia
Structure of Thr 160 phosphorylated CDK2/cyclin A in complex with the inhibitor NU6271
Structural highlights
FunctionCCNA2_BOVIN Essential for the control of the cell cycle at the G1/S (start) and the G2/M (mitosis) transitions. Evolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedbeta-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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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