2r3f: Difference between revisions
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'''Crystal Structure of Cyclin-Dependent Kinase 2 with inhibitor''' | {{Structure | ||
|PDB= 2r3f |SIZE=350|CAPTION= <scene name='initialview01'>2r3f</scene>, resolution 1.50Å | |||
|SITE= <scene name='pdbsite=AC1:Ace+Binding+Site+For+Residue+A+0'>AC1</scene> and <scene name='pdbsite=AC2:Sc8+Binding+Site+For+Residue+A+501'>AC2</scene> | |||
|LIGAND= <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene> and <scene name='pdbligand=SC8:'>SC8</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Cyclin-dependent_kinase Cyclin-dependent kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.22 2.7.11.22] | |||
|GENE= CDK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Crystal Structure of Cyclin-Dependent Kinase 2 with inhibitor''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2R3F is a [ | 2R3F is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R3F OCA]. | ||
==Reference== | ==Reference== | ||
Structure-guided discovery of cyclin-dependent kinase inhibitors., Fischmann TO, Hruza A, Duca JS, Ramanathan L, Mayhood T, Windsor WT, Le HV, Guzi TJ, Dwyer MP, Paruch K, Doll RJ, Lees E, Parry D, Seghezzi W, Madison V, Biopolymers. 2007 Oct 15;. PMID:[http:// | Structure-guided discovery of cyclin-dependent kinase inhibitors., Fischmann TO, Hruza A, Duca JS, Ramanathan L, Mayhood T, Windsor WT, Le HV, Guzi TJ, Dwyer MP, Paruch K, Doll RJ, Lees E, Parry D, Seghezzi W, Madison V, Biopolymers. 2007 Oct 15;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17937404 17937404] | ||
[[Category: Cyclin-dependent kinase]] | [[Category: Cyclin-dependent kinase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:32:12 2008'' | ||
Revision as of 19:32, 20 March 2008
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| , resolution 1.50Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | and | ||||||
| Ligands: | and | ||||||
| Gene: | CDK2 (Homo sapiens) | ||||||
| Activity: | Cyclin-dependent kinase, with EC number 2.7.11.22 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of Cyclin-Dependent Kinase 2 with inhibitor
OverviewOverview
CDK2 inhibitors containing the related bicyclic heterocycles pyrazolopyrimidines and imidazopyrazines were discovered through high-throughput screening. Crystal structures of inhibitors with these bicyclic cores and two more related ones show that all but one have a common binding mode featuring two hydrogen bonds (H-bonds) to the backbone of the kinase hinge region. Even though ab initio computations indicated that the imidazopyrazine core would bind more tightly to the hinge, pyrazolopyrimidines gain an advantage in potency through participation of N4 in an H-bond network involving two catalytic residues and bridging water molecules. Further insight into inhibitor/CDK2 interactions was gained from analysis of additional crystal structures. Significant gains in potency were obtained by optimizing the fit of hydrophobic substituents to the gatekeeper region of the ATP binding site. The most potent inhibitors have good selectivity. (c) 2007 Wiley Periodicals, Inc. Biopolymers, 2007.
About this StructureAbout this Structure
2R3F is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structure-guided discovery of cyclin-dependent kinase inhibitors., Fischmann TO, Hruza A, Duca JS, Ramanathan L, Mayhood T, Windsor WT, Le HV, Guzi TJ, Dwyer MP, Paruch K, Doll RJ, Lees E, Parry D, Seghezzi W, Madison V, Biopolymers. 2007 Oct 15;. PMID:17937404
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