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PDBsum entry 4cwp
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PDB id:
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Chaperone
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Title:
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Human hsp90 alpha n-terminal domain in complex with an aminotriazoloquinazoline inhibitor
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Structure:
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Heat shock protein hsp 90-alpha. Chain: a. Fragment: n-terminal domain, residues 9-236. Synonym: heat shock 86 kda, hsp 86, hsp86, renal carcinoma antigen ny-ren-38. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693.
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Resolution:
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1.95Å
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R-factor:
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0.201
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R-free:
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0.216
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Authors:
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E.Casale,N.Amboldi,G.Brasca,D.Caronni,N.Colombo,C.Dalvit,E.R.Felder, G.Fogliatto,A.Isacchi,S.Mantegani,P.Polucci,L.Riceputi,F.Sola, C.Visco,F.Zuccotto,F.Casuscelli
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Key ref:
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E.Casale
et al.
(2014).
Fragment-based hit discovery and structure-based optimization of aminotriazoloquinazolines as novel Hsp90 inhibitors.
Bioorg Med Chem Lett,
22,
4135-4150.
PubMed id:
DOI:
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Date:
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03-Apr-14
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Release date:
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09-Jul-14
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PROCHECK
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Headers
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References
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P07900
(HS90A_HUMAN) -
Heat shock protein HSP 90-alpha from Homo sapiens
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Seq:
Struc:
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732 a.a.
207 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.3.6.4.10
- non-chaperonin molecular chaperone ATPase.
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Reaction:
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ATP + H2O = ADP + phosphate + H+
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ATP
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+
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H2O
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=
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ADP
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+
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phosphate
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Bioorg Med Chem Lett
22:4135-4150
(2014)
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PubMed id:
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Fragment-based hit discovery and structure-based optimization of aminotriazoloquinazolines as novel Hsp90 inhibitors.
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E.Casale,
N.Amboldi,
M.G.Brasca,
D.Caronni,
N.Colombo,
C.Dalvit,
E.R.Felder,
G.Fogliatto,
A.Galvani,
A.Isacchi,
P.Polucci,
L.Riceputi,
F.Sola,
C.Visco,
F.Zuccotto,
F.Casuscelli.
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ABSTRACT
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In the last decade the heat shock protein 90 (Hsp90) has emerged as a major
therapeutic target and many efforts have been dedicated to the discovery of
Hsp90 inhibitors as new potent anticancer agents. Here we report the
identification of a novel class of Hsp90 inhibitors by means of a biophysical
FAXS-NMR based screening of a library of fragments. The use of X-ray structure
information combined with modeling studies enabled the fragment evolution of the
initial triazoloquinazoline hit to a class of compounds with nanomolar potency
and drug-like properties suited for further lead optimization.
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