3D0B

Crystal Structure of Benzamide Tetrahydro-4H-carbazol-4-one bound to Hsp90

Summary for 3D0B

• Entry DOI: 10.2210/pdb3d0b/pdb
• Descriptor: Heat shock protein HSP 90-alpha, 2-[(2-methoxyethyl)amino]-4-(4-oxo-1,2,3,4-tetrahydro-9H-carbazol-9-yl)benzamide (3 entities in total)
• Functional Keywords: hsp90, heat shock protein 90, alternative splicing, atp-binding, chaperone, cytoplasm, nucleotide-binding, phosphoprotein, stress response
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P07900
• Total number of polymer chains: 1
• Total formula weight: 26534.82

Authors

Barta, T.E.,Veal, J.M.,Huang, K.H.,Hall, S.H. (deposition date: 2008-05-01, release date: 2008-06-17, Last modification date: 2024-04-10)

Primary citation

Barta, T.E.,Veal, J.M.,Rice, J.W.,Partridge, J.M.,Fadden, R.P.,Ma, W.,Jenks, M.,Geng, L.,Hanson, G.J.,Huang, K.H.,Barabasz, A.F.,Foley, B.E.,Otto, J.,Hall, S.E.
Discovery of benzamide tetrahydro-4H-carbazol-4-ones as novel small molecule inhibitors of Hsp90
BIOORG.MED.CHEM.LETT., 18:3517-3521, 2008

PubMed Abstract: Hsp90 maintains the conformational stability of multiple proteins implicated in oncogenesis and has emerged as a target for chemotherapy. We report here the discovery of a novel small molecule scaffold that inhibits Hsp90. X-ray data show that the scaffold binds competitively at the ATP site on Hsp90. Cellular proliferation and client assays demonstrate that members of the series are able to inhibit Hsp90 at nanomolar concentrations.

PubMed: 18511277
DOI: 10.1016/j.bmcl.2008.05.023

Experimental method

X-RAY DIFFRACTION (1.74 Å)