1h1r: Difference between revisions

Revision as of 06:28, 1 July 2008

This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.

File:1h1r.png

Template:STRUCTURE 1h1r

STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/CYCLIN A COMPLEXED WITH THE INHIBITOR NU6086STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/CYCLIN A COMPLEXED WITH THE INHIBITOR NU6086

Template:ABSTRACT PUBMED 12244298

About this StructureAbout this Structure

1H1R is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor., Davies TG, Bentley J, Arris CE, Boyle FT, Curtin NJ, Endicott JA, Gibson AE, Golding BT, Griffin RJ, Hardcastle IR, Jewsbury P, Johnson LN, Mesguiche V, Newell DR, Noble ME, Tucker JA, Wang L, Whitfield HJ, Nat Struct Biol. 2002 Oct;9(10):745-9. PMID:12244298

Page seeded by OCA on Tue Jul 1 06:28:34 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:1h1r.gif|left|200px]]
+{{Seed}}
+[[Image:1h1r.png|left|200px]]
 <!--
@@ Line 9: / Line 10: @@
 {{STRUCTURE_1h1r|  PDB=1h1r  |  SCENE=  }}
-'''STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/CYCLIN A COMPLEXED WITH THE INHIBITOR NU6086'''
+===STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/CYCLIN A COMPLEXED WITH THE INHIBITOR NU6086===
-==Overview==
+<!--
-Aberrant control of cyclin-dependent kinases (CDKs) is a central feature of the molecular pathology of cancer. Iterative structure-based design was used to optimize the ATP- competitive inhibition of CDK1 and CDK2 by O(6)-cyclohexylmethylguanines, resulting in O(6)-cyclohexylmethyl-2-(4'- sulfamoylanilino)purine. The new inhibitor is 1,000-fold more potent than the parent compound (K(i) values for CDK1 = 9 nM and CDK2 = 6 nM versus 5,000 nM and 12,000 nM, respectively, for O(6)-cyclohexylmethylguanine). The increased potency arises primarily from the formation of two additional hydrogen bonds between the inhibitor and Asp 86 of CDK2, which facilitate optimum hydrophobic packing of the anilino group with the specificity surface of CDK2. Cellular studies with O(6)-cyclohexylmethyl-2-(4'- sulfamoylanilino) purine demonstrated inhibition of MCF-7 cell growth and target protein phosphorylation, consistent with CDK1 and CDK2 inhibition. The work represents the first successful iterative synthesis of a potent CDK inhibitor based on the structure of fully activated CDK2-cyclin A. Furthermore, the potency of O(6)-cyclohexylmethyl-2-(4'- sulfamoylanilino)purine was both predicted and fully rationalized on the basis of protein-ligand interactions.
+The line below this paragraph, {{ABSTRACT_PUBMED_12244298}}, adds the Publication Abstract to the page
+(as it appears on PubMed at http://www.pubmed.gov), where 12244298 is the PubMed ID number.
+-->
+{{ABSTRACT_PUBMED_12244298}}
 ==About this Structure==
@@ Line 34: / Line 38: @@
 [[Category: Serine/threonine-protein kinase]]
 [[Category: Transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 18:18:31 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul  1 06:28:34 2008''