Linked Life Data

11170642

Source:http://linkedlifedata.com/resource/pubmed/id/11170642

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-2-22
pubmed:abstractText
Cyclin-dependent kinases (CDKs) are regulatory proteins of the eukaryotic cell cycle. They act after association with different cyclins, the concentrations of which vary throughout the progression of the cell cycle. As central mediators of cell growth, CDKs are potential targets for inhibitory molecules that would allow disruption of the cell cycle in order to evoke an antiproliferative effect and may therefore be useful as cancer therapeutics. We synthesized several inhibitory 2,6,9-trisubstituted purine derivatives and solved the crystal structure of one of these compounds, H717, in complex with human CDK2 at 2.6 A resolution. The orientation of the C2-p-diaminocyclohexyl portion of the inhibitor is strikingly different from those of similar moieties in other related inhibitor complexes. The N9-cyclopentyl ring fully occupies a space in the enzyme which is otherwise empty, while the C6-N-aminobenzyl substituent points out of the ATP-binding site. The structure provides a basis for the further development of more potent inhibitory drugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
524-30
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Crystal structure of human cyclin-dependent kinase 2 in complex with the adenine-derived inhibitor H717.
pubmed:affiliation
Department of Chemistry and Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA. dreyer@biozentrum.uni.wuerzburg.de
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't