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PDBsum entry 3d0b
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protein ligands links
Chaperone PDB id
3d0b

 

 

 

 

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Contents
Protein chain
208 a.a. *
Ligands
SNX
Waters ×282
* Residue conservation analysis
PDB id:
3d0b
Name: Chaperone
Title: Crystal structure of benzamide tetrahydro-4h-carbazol-4-one bound to hsp90
Structure: Heat shock protein hsp 90-alpha. Chain: a. Fragment: n-terminal domain residues 1-232. Synonym: hsp 86, renal carcinoma antigen ny- ren-38
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
1.74Å     R-factor:   0.202     R-free:   0.228
Authors: T.E.Barta,J.M.Veal,K.H.Huang,S.H.Hall
Key ref: T.E.Barta et al. (2008). Discovery of benzamide tetrahydro-4H-carbazol-4-ones as novel small molecule inhibitors of Hsp90. Bioorg Med Chem Lett, 18, 3517-3521. PubMed id: 18511277
Date:
01-May-08     Release date:   17-Jun-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P07900  (HS90A_HUMAN) -  Heat shock protein HSP 90-alpha from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		732 a.a.
208 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.6.4.10  - non-chaperonin molecular chaperone ATPase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + H2O = ADP + phosphate + H+
ATP
 + H2O
 = ADP
 + phosphate
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
Bioorg Med Chem Lett 18:3517-3521 (2008)
PubMed id: 18511277  
 
 
Discovery of benzamide tetrahydro-4H-carbazol-4-ones as novel small molecule inhibitors of Hsp90.
T.E.Barta, J.M.Veal, J.W.Rice, J.M.Partridge, R.P.Fadden, W.Ma, M.Jenks, L.Geng, G.J.Hanson, K.H.Huang, A.F.Barabasz, B.E.Foley, J.Otto, S.E.Hall.
 
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21420297 C.W.Zapf, J.D.Bloom, J.L.McBean, R.G.Dushin, T.Nittoli, C.Ingalls, A.G.Sutherland, J.P.Sonye, C.N.Eid, J.Golas, H.Liu, F.Boschelli, Y.Hu, E.Vogan, and J.I.Levin (2011).
Design and SAR of macrocyclic Hsp90 inhibitors with increased metabolic stability and potent cell-proliferation activity.
  Bioorg Med Chem Lett, 21, 2278-2282.
PDB code: 3qtf
21515049 C.W.Zapf, J.D.Bloom, J.L.McBean, R.G.Dushin, T.Nittoli, M.Otteng, C.Ingalls, J.M.Golas, H.Liu, J.Lucas, F.Boschelli, Y.Hu, E.Vogan, and J.I.Levin (2011).
Macrocyclic lactams as potent Hsp90 inhibitors with excellent tumor exposure and extended biomarker activity.
  Bioorg Med Chem Lett, 21, 3411-3416.
PDB code: 3r91
21531051 S.Sakkiah, S.Thangapandian, S.John, and K.W.Lee (2011).
Pharmacophore based virtual screening, molecular docking studies to design potent heat shock protein 90 inhibitors.
  Eur J Med Chem, 46, 2937-2947.  
21459002 T.Taldone, D.Zatorska, P.D.Patel, H.Zong, A.Rodina, J.H.Ahn, K.Moulick, M.L.Guzman, and G.Chiosis (2011).
Design, synthesis, and evaluation of small molecule Hsp90 probes.
  Bioorg Med Chem, 19, 2603-2614.  
20659681 P.Fadden, K.H.Huang, J.M.Veal, P.M.Steed, A.F.Barabasz, B.Foley, M.Hu, J.M.Partridge, J.Rice, A.Scott, L.G.Dubois, T.A.Freed, M.A.Silinski, T.E.Barta, P.F.Hughes, A.Ommen, W.Ma, E.D.Smith, A.W.Spangenberg, J.Eaves, G.J.Hanson, L.Hinkley, M.Jenks, M.Lewis, J.Otto, G.J.Pronk, K.Verleysen, T.A.Haystead, and S.E.Hall (2010).
Application of chemoproteomics to drug discovery: identification of a clinical candidate targeting hsp90.
  Chem Biol, 17, 686-694.
PDB code: 3mnr
19934398 P.Putcha, K.M.Danzer, L.R.Kranich, A.Scott, M.Silinski, S.Mabbett, C.D.Hicks, J.M.Veal, P.M.Steed, B.T.Hyman, and P.J.McLean (2010).
Brain-permeable small-molecule inhibitors of Hsp90 prevent alpha-synuclein oligomer formation and rescue alpha-synuclein-induced toxicity.
  J Pharmacol Exp Ther, 332, 849-857.  
19212985 J.Chen, J.Lou, T.Liu, R.Wu, X.Dong, Q.He, B.Yang, and Y.Hu (2009).
Synthesis and in-vitro antitumor activities of some mannich bases of 9-alkyl-1,2,3,4-tetrahydrocarbazole-1-ones.
  Arch Pharm (Weinheim), 342, 165-172.  
19685544 M.Sgobba, and G.Rastelli (2009).
Structure-based and in silico design of Hsp90 inhibitors.
  ChemMedChem, 4, 1399-1409.  
19171973 R.P.Joosten, T.Womack, G.Vriend, and G.Bricogne (2009).
Re-refinement from deposited X-ray data can deliver improved models for most PDB entries.
  Acta Crystallogr D Biol Crystallogr, 65, 176-185.  
19856365 S.Barluenga, J.G.Fontaine, C.Wang, K.Aouadi, R.Chen, K.Beebe, L.Neckers, and N.Winssinger (2009).
Inhibition of HSP90 with pochoximes: SAR and structure-based insights.
  Chembiochem, 10, 2753-2759.
PDB codes: 3inw 3inx
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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