1ol2: Difference between revisions

Revision as of 03:59, 3 May 2008

CYCLIN A BINDING GROOVE INHIBITOR H-ARG-ARG-LEU-ASN-(P-F-PHE)-NH2

OverviewOverview

Inhibition of CDK2/CA (cyclin-dependent kinase 2/cyclin A complex) activity through blocking of the substrate recognition site in the cyclin A subunit has been demonstrated to be an effective method for inducing apoptosis in tumor cells. We have used the cyclin binding motif (CBM) present in the tumor suppressor proteins p21(WAF1) and p27(KIP1) as a template to optimize the minimal sequence necessary for CDK2/CA inhibition. A series of peptides were prepared, containing nonnatural amino acids, which possess nano- to micromolar CDK2-inhibitory activity. Here we present X-ray structures of the protein complex CDK2/CA, together with the cyclin groove-bound peptides H-Ala-Ala-Abu-Arg-Ser-Leu-Ile-(p-F-Phe)-NH(2) (peptide 1), H-Arg-Arg-Leu-Ile-Phe-NH(2) (peptide 2), Ac-Arg-Arg-Leu-Asn-(m-Cl-Phe)-NH(2) (peptide 3), H-Arg-Arg-Leu-Asn-(p-F-Phe)-NH(2) (peptide 4), and H-Cit-Cit-Leu-Ile-(p-F-Phe)-NH(2) (peptide 5). Some of the peptide complexes presented here were obtained through the novel technique of ligand exchange within protein crystals. This method may find general application for obtaining complex structures of proteins with surface-bound ligands.

About this StructureAbout this Structure

1OL2 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Insights into cyclin groove recognition: complex crystal structures and inhibitor design through ligand exchange., Kontopidis G, Andrews MJ, McInnes C, Cowan A, Powers H, Innes L, Plater A, Griffiths G, Paterson D, Zheleva DI, Lane DP, Green S, Walkinshaw MD, Fischer PM, Structure. 2003 Dec;11(12):1537-46. PMID:14656438 Page seeded by OCA on Sat May 3 03:59:23 2008

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

OCA

@@ Line 1: / Line 1: @@
 [[Image:1ol2.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1ol2 |SIZE=350|CAPTION= <scene name='initialview01'>1ol2</scene>, resolution 2.6&Aring;
+The line below this paragraph, containing "STRUCTURE_1ol2", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=CBB:Cyclin+Binding+Groove+Chain+D'>CBB</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PFF:4-FLUORO-L-PHENYLALANINE'>PFF</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=
+-->
-|DOMAIN=
+{{STRUCTURE_1ol2|  PDB=1ol2  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ol2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ol2 OCA], [http://www.ebi.ac.uk/pdbsum/1ol2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ol2 RCSB]</span>
-}}
 '''CYCLIN A BINDING GROOVE INHIBITOR H-ARG-ARG-LEU-ASN-(P-F-PHE)-NH2'''
@@ Line 40: / Line 37: @@
 [[Category: Walkinshaw, M.]]
 [[Category: Zheleva, D.]]
-[[Category: cyclin some]]
+[[Category: Cyclin some]]
-[[Category: drug design]]
+[[Category: Drug design]]
-[[Category: inhibitor]]
+[[Category: Inhibitor]]
-[[Category: kinase]]
+[[Category: Kinase]]
-[[Category: ligand exchange]]
+[[Category: Ligand exchange]]
-[[Category: peptidomimetic]]
+[[Category: Peptidomimetic]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 03:59:23 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:46:50 2008''