1pf8: Difference between revisions

Revision as of 05:00, 3 May 2008

Crystal Structure of Human Cyclin-Dependent Kinase 2 Complexed with a Nucleoside Inhibitor

OverviewOverview

SU9516 is a 3-substituted indolinone compound with demonstrated potent and selective inhibition toward cyclin dependent kinases (cdks). Here, we describe the kinetic characterization of this inhibition with respect to cdk2, 1, and 4, along with the crystal structure in complex with cdk2. The molecule is competitive with respect to ATP for cdk2/cyclin A, with a K(i) value of 0.031 microM. Similarly, SU9516 inhibits cdk2/cyclin E and cdk1/cyclin B1 in an ATP-competitive manner, although at a 2- to 8-fold reduced potency. In contrast, the compound exhibited non-competitive inhibition with respect to ATP toward cdk4/cyclin D1, with a 45-fold reduced potency. The X-ray crystal structure of SU9516 bound to cdk2 revealed interactions between the molecule and Leu83 and Glu81 of the kinase. This study should aid in the development of more potent and selective cdk inhibitors for potential therapeutic agents.

About this StructureAbout this Structure

1PF8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

SU9516: biochemical analysis of cdk inhibition and crystal structure in complex with cdk2., Moshinsky DJ, Bellamacina CR, Boisvert DC, Huang P, Hui T, Jancarik J, Kim SH, Rice AG, Biochem Biophys Res Commun. 2003 Oct 24;310(3):1026-31. PMID:14550307 Page seeded by OCA on Sat May 3 05:00:56 2008

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OCA

@@ Line 1: / Line 1: @@
 [[Image:1pf8.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1pf8 |SIZE=350|CAPTION= <scene name='initialview01'>1pf8</scene>, resolution 2.51&Aring;
+The line below this paragraph, containing "STRUCTURE_1pf8", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=SU9:(3Z)-3-(1H-IMIDAZOL-5-YLMETHYLENE)-5-METHOXY-1H-INDOL-2(3H)-ONE'>SU9</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|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>
+or leave the SCENE parameter empty for the default display.
-|GENE= CDK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_1pf8|  PDB=1pf8  |  SCENE=  }}
-|RELATEDENTRY=[[1hck|1HCK]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pf8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pf8 OCA], [http://www.ebi.ac.uk/pdbsum/1pf8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pf8 RCSB]</span>
-}}
 '''Crystal Structure of Human Cyclin-Dependent Kinase 2 Complexed with a Nucleoside Inhibitor'''
@@ Line 34: / Line 31: @@
 [[Category: Moshinsky, D J.]]
 [[Category: Rice, A G.]]
-[[Category: atp-binding]]
+[[Category: Atp-binding]]
-[[Category: cell cycle]]
+[[Category: Cell cycle]]
-[[Category: cell division]]
+[[Category: Cell division]]
-[[Category: inhibitor]]
+[[Category: Inhibitor]]
-[[Category: mitosis]]
+[[Category: Mitosis]]
-[[Category: phosphorylation]]
+[[Category: Phosphorylation]]
-[[Category: serine/threonine protein kinase]]
+[[Category: Serine/threonine protein kinase]]
-[[Category: su9516]]
+[[Category: Su9516]]
-[[Category: transferase]]
+[[Category: Transferase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 05:00:56 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:58:49 2008''