2cdd: Difference between revisions

Revision as of 21:52, 3 May 2008

HUMAN HSP90 WITH 4-(4-(2,3-DIHYDRO-BENZOL(1,4)DIOXIN-6-YL)-5-METHYL-1H-PYRAZOL-3-YL)-6-ETHYL-BENZENE-1,3-DIOL

OverviewOverview

Hsp90 encodes a ubiquitous molecular chaperone protein conserved among species which acts on multiple substrates, many of which are important cell-signaling proteins. Inhibition of Hsp90 function has been promoted as a mechanism to degrade client proteins involved in tumorigenesis and disease progression. Several assays to monitor inhibition of Hsp90 function currently exist but are limited in their use for a drug discovery campaign. Using data from the crystal structure of an initial hit compound, we have developed a fluorescence polarization assay to monitor binding of compounds to the ATP-binding site of Hsp90. This assay is very robust (Z' > 0.9) and can detect affinity of compounds with IC50s to 40 nM. We have used this assay in conjunction with cocrystal structures of small molecules to drive a structure-based design program aimed at the discovery and optimization of a novel class of potent Hsp90 inhibitors.

About this StructureAbout this Structure

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

ReferenceReference

A fluorescence polarization assay for inhibitors of Hsp90., Howes R, Barril X, Dymock BW, Grant K, Northfield CJ, Robertson AG, Surgenor A, Wayne J, Wright L, James K, Matthews T, Cheung KM, McDonald E, Workman P, Drysdale MJ, Anal Biochem. 2006 Mar 15;350(2):202-13. Epub 2006 Jan 23. PMID:16460658 Page seeded by OCA on Sat May 3 21:52:28 2008

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

OCA

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 [[Image:2cdd.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2cdd |SIZE=350|CAPTION= <scene name='initialview01'>2cdd</scene>, resolution 1.90&Aring;
+The line below this paragraph, containing "STRUCTURE_2cdd", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Ct5+Binding+Site+For+Chain+B'>AC1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=CT5:4-[4-(2,3-DIHYDRO-1,4-BENZODIOXIN-6-YL)-3-METHYL-1H-PYRAZOL-5-YL]-6-ETHYLBENZENE-1,3-DIOL'>CT5</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY=
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_2cdd|  PDB=2cdd  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2cdd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cdd OCA], [http://www.ebi.ac.uk/pdbsum/2cdd PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2cdd RCSB]</span>
-}}
 '''HUMAN HSP90 WITH 4-(4-(2,3-DIHYDRO-BENZOL(1,4)DIOXIN-6-YL)-5-METHYL-1H-PYRAZOL-3-YL)-6-ETHYL-BENZENE-1,3-DIOL'''
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 [[Category: Workman, P.]]
 [[Category: Wright, L.]]
-[[Category: atp-binding]]
+[[Category: Atp-binding]]
-[[Category: atpase]]
+[[Category: Atpase]]
-[[Category: chaperone]]
+[[Category: Chaperone]]
-[[Category: heat shock]]
+[[Category: Heat shock]]
-[[Category: hsp90]]
+[[Category: Hsp90]]
-[[Category: nucleotide-binding]]
+[[Category: Nucleotide-binding]]
-[[Category: phosphorylation]]
+[[Category: Phosphorylation]]
-[[Category: pyrazole]]
+[[Category: Pyrazole]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 21:52:28 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:19:57 2008''