1ke5: Difference between revisions
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=LS1:N-METHYL-4-{[(2-OXO-1,2-DIHYDRO-3H-INDOL-3-YLIDENE)METHYL]AMINO}BENZENESULFONAMIDE'>LS1</scene> | |LIGAND= <scene name='pdbligand=LS1:N-METHYL-4-{[(2-OXO-1,2-DIHYDRO-3H-INDOL-3-YLIDENE)METHYL]AMINO}BENZENESULFONAMIDE'>LS1</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1ke6|1KE6]], [[1ke7|1KE7]], [[1ke8|1KE8]], [[1ke9|1KE9]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ke5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ke5 OCA], [http://www.ebi.ac.uk/pdbsum/1ke5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ke5 RCSB]</span> | |||
}} | }} | ||
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[[Category: Kuyper, L F.]] | [[Category: Kuyper, L F.]] | ||
[[Category: Shewchuk, L M.]] | [[Category: Shewchuk, L M.]] | ||
[[Category: cyclin kinase]] | [[Category: cyclin kinase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:47:16 2008'' | ||
Revision as of 21:47, 30 March 2008
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| , resolution 2.20Å | |||||||
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| Ligands: | |||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Related: | 1KE6, 1KE7, 1KE8, 1KE9
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CDK2 complexed with N-methyl-4-{[(2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]amino}benzenesulfonamide
OverviewOverview
Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepared as a homologue of the 3-benzylidene-1,3-dihydro-2H-indol-2-one class of kinase inhibitor. Crystallographic analysis of the lead compound bound to CDK2 provided the basis for analogue design. A semiautomated method of ligand docking was used to select compounds for synthesis, and a number of compounds with low nanomolar inhibitory activity versus CDK2 were identified. Enzyme binding determinants for several analogues were evaluated by X-ray crystallography. Compounds in this series inhibited CDK2 with a potency approximately 10-fold greater than that for CDK1. Members of this class of inhibitor cause an arrest of the cell cycle and have shown potential utility in the prevention of chemotherapy-induced alopecia.
About this StructureAbout this Structure
1KE5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis., Bramson HN, Corona J, Davis ST, Dickerson SH, Edelstein M, Frye SV, Gampe RT Jr, Harris PA, Hassell A, Holmes WD, Hunter RN, Lackey KE, Lovejoy B, Luzzio MJ, Montana V, Rocque WJ, Rusnak D, Shewchuk L, Veal JM, Walker DH, Kuyper LF, J Med Chem. 2001 Dec 6;44(25):4339-58. PMID:11728181
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