1ke7: Difference between revisions

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Revision as of 13:16, 20 March 2008

File:1ke7.jpg

, resolution 2.0Å

Ligands:

Activity:

Non-specific serine/threonine protein kinase, with EC number 2.7.11.1

Coordinates:

save as pdb, mmCIF, xml

CYCLIN-DEPENDENT KINASE 2 (CDK2) COMPLEXED WITH 3-{[(2,2-DIOXIDO-1,3-DIHYDRO-2-BENZOTHIEN-5-YL)AMINO]METHYLENE}-5-(1,3-OXAZOL-5-YL)-1,3-DIHYDRO-2H-INDOL-2-ONE

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

1KE7 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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OCA

@@ Line 1: / Line 1: @@
-[[Image:1ke7.jpg|left|200px]]<br /><applet load="1ke7" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:1ke7.jpg|left|200px]]
-caption="1ke7, resolution 2.0&Aring;" />
-'''CYCLIN-DEPENDENT KINASE 2 (CDK2) COMPLEXED WITH 3-{[(2,2-DIOXIDO-1,3-DIHYDRO-2-BENZOTHIEN-5-YL)AMINO]METHYLENE}-5-(1,3-OXAZOL-5-YL)-1,3-DIHYDRO-2H-INDOL-2-ONE'''<br />
+ {{Structure
+|PDB= 1ke7 |SIZE=350|CAPTION= <scene name='initialview01'>1ke7</scene>, resolution 2.0&Aring;
+|SITE=
+|LIGAND= <scene name='pdbligand=LS3:3-{[(2,2-DIOXIDO-1,3-DIHYDRO-2-BENZOTHIEN-5-YL)AMINO]METHYLENE}-5-(1,3-OXAZOL-5-YL)-1,3-DIHYDRO-2H-INDOL-2-ONE'>LS3</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]
+|GENE=
+}}
+'''CYCLIN-DEPENDENT KINASE 2 (CDK2) COMPLEXED WITH 3-{[(2,2-DIOXIDO-1,3-DIHYDRO-2-BENZOTHIEN-5-YL)AMINO]METHYLENE}-5-(1,3-OXAZOL-5-YL)-1,3-DIHYDRO-2H-INDOL-2-ONE'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-KE7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=LS3:'>LS3</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KE7 OCA].
+KE7 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=1KE7 OCA].
 ==Reference==
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11728181 11728181]
+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:[http://www.ncbi.nlm.nih.gov/pubmed/11728181 11728181]
 [[Category: Homo sapiens]]
 [[Category: Non-specific serine/threonine protein kinase]]
@@ Line 28: / Line 37: @@
 [[Category: kinase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:33:06 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:16:19 2008''