2a0c: Difference between revisions

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Revision as of 01:46, 31 March 2008

File:2a0c.gif

, resolution 1.95Å

Ligands:

Gene:

CDK2 (Homo sapiens)

Activity:

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

Resources:

FirstGlance, OCA, PDBsum, RCSB

Coordinates:

save as pdb, mmCIF, xml

Human CDK2 in complex with olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor

OverviewOverview

The study describes the protein kinase selectivity profile, as well as the binding mode of olomoucine II in the catalytic cleft of CDK2, as determined from cocrystal analysis. Apart from the main cell cycle-regulating kinase CDK2, olomoucine II exerts specificity for CDK7 and CDK9, with important functions in the regulation of RNA transcription. In vitro anticancer activity of the inhibitor in a panel of tumor cell lines shows a wide potency range with a slight preference for cells harboring a wild-type p53 gene. Cell-based assays confirmed activation of p53 protein levels and events leading to accumulation of p21(WAF1). Additionally, in olomoucine II-treated cells, Mdm2 was found to form a complex with the ribosomal protein L11, which inhibits Mdm2 ubiquitin ligase function. We conclude that perturbations in RNA synthesis may lead to activation of p53 and that this contributes to the antiproliferative potency of cyclindependent kinase inhibitors.

About this StructureAbout this Structure

2A0C is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor., Krystof V, McNae IW, Walkinshaw MD, Fischer PM, Muller P, Vojtesek B, Orsag M, Havlicek L, Strnad M, Cell Mol Life Sci. 2005 Aug;62(15):1763-71. PMID:16003486

Page seeded by OCA on Mon Mar 31 01:46:14 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 5: / Line 5: @@
 |SITE=
 |LIGAND= <scene name='pdbligand=CK9:2-{[(2-{[(1R)-1-(HYDROXYMETHYL)PROPYL]AMINO}-9-ISOPROPYL-9H-PURIN-6-YL)AMINO]METHYL}PHENOL'>CK9</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= CDK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+|DOMAIN=
+|RELATEDENTRY=
+|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a0c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a0c OCA], [http://www.ebi.ac.uk/pdbsum/2a0c PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2a0c RCSB]</span>
 }}
@@ Line 32: / Line 35: @@
 [[Category: Vojtesek, B.]]
 [[Category: Walkinshaw, M D.]]
-[[Category: CK9]]
 [[Category: 3d-structure]]
 [[Category: atp-binding]]
 [[Category: cell cycle]]
-[[Category: cell division]]
+[[Category: cell division,mitosis]]
 [[Category: inhibition]]
-[[Category: mitosis]]
 [[Category: phosphorylation]]
 [[Category: protein kinase]]
@@ Line 44: / Line 45: @@
 [[Category: transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:43:58 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:46:14 2008''