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PDBsum entry 2byh
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Contents |
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* Residue conservation analysis
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PDB id:
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Chaperone
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Title:
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3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as inhibitors of the hsp90 molecular chaperone
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Structure:
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Heat shock protein hsp90-alpha. Chain: a. Fragment: n-terminal domain, residues 1-235. Synonym: hsp 86. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Organ: skin. Tissue: melanoma. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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1.90Å
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R-factor:
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0.169
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R-free:
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0.211
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Authors:
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P.A.Brough,X.Barril,M.Beswick,B.W.Dymock,M.J.Drysdale,L.Wright, K.Grant,A.Massey,A.Surgenor,P.Workman
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Key ref:
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P.A.Brough
et al.
(2005).
3-(5-Chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone.
Bioorg Med Chem Lett,
15,
5197-5201.
PubMed id:
DOI:
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Date:
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02-Aug-05
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Release date:
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12-Oct-05
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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.
215 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
15:5197-5201
(2005)
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PubMed id:
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3-(5-Chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone.
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P.A.Brough,
X.Barril,
M.Beswick,
B.W.Dymock,
M.J.Drysdale,
L.Wright,
K.Grant,
A.Massey,
A.Surgenor,
P.Workman.
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ABSTRACT
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Information from X-ray crystal structures of Hsp90 inhibitors bound to the human
Hsp90 molecular chaperone was used to assist in the design of
3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as novel inhibitors of
Hsp90. Accessing an extra interaction with the protein via Phe138 gave a
significant increase in binding potency compared to similar analogues that do
not make this interaction.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.Niewiadomy,
J.Matysiak,
and
M.M.Karpińska
(2011).
Synthesis and Anticancer Activity of New 2-Aryl-4H-3,1-benzothiazines.
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Arch Pharm (Weinheim),
344,
224-230.
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J.Matysiak,
A.Niewiadomy,
B.Paw,
and
I.Dybała
(2011).
NMR QSAR model for the analysis of 4-(5-arylamino-1,3,4-thiadiazol-2-yl)benzene-1,3-diols.
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Arch Pharm (Weinheim),
344,
340-344.
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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.
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Eur J Med Chem,
46,
2937-2947.
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M.Sgobba,
and
G.Rastelli
(2009).
Structure-based and in silico design of Hsp90 inhibitors.
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ChemMedChem,
4,
1399-1409.
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N.Gaspar,
S.Y.Sharp,
S.Pacey,
C.Jones,
M.Walton,
G.Vassal,
S.Eccles,
A.Pearson,
and
P.Workman
(2009).
Acquired resistance to 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) in glioblastoma cells.
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Cancer Res,
69,
1966-1975.
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R.M.Immormino,
L.E.Metzger,
P.N.Reardon,
D.E.Dollins,
B.S.Blagg,
and
D.T.Gewirth
(2009).
Different poses for ligand and chaperone in inhibitor-bound Hsp90 and GRP94: implications for paralog-specific drug design.
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J Mol Biol,
388,
1033-1042.
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PDB codes:
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T.Taldone,
W.Sun,
and
G.Chiosis
(2009).
Discovery and development of heat shock protein 90 inhibitors.
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Bioorg Med Chem,
17,
2225-2235.
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V.Giansanti,
T.Camboni,
F.Piscitelli,
E.Prosperi,
G.La Regina,
M.C.Lazzè,
G.Santin,
R.Silvestri,
and
A.I.Scovassi
(2009).
Study of the effects of a new pyrazolecarboxamide: changes in mitochondria and induction of apoptosis.
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Int J Biochem Cell Biol,
41,
1890-1898.
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C.S.McErlean,
N.Proisy,
C.J.Davis,
N.A.Boland,
S.Y.Sharp,
K.Boxall,
A.M.Slawin,
P.Workman,
and
C.J.Moody
(2007).
Synthetic ansamycins prepared by a ring-expanding Claisen rearrangement. Synthesis and biological evaluation of ring and conformational analogues of the Hsp90 molecular chaperone inhibitor geldanamycin.
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Org Biomol Chem,
5,
531-546.
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L.Galam,
M.K.Hadden,
Z.Ma,
Q.Z.Ye,
B.G.Yun,
B.S.Blagg,
and
R.L.Matts
(2007).
High-throughput assay for the identification of Hsp90 inhibitors based on Hsp90-dependent refolding of firefly luciferase.
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Bioorg Med Chem,
15,
1939-1946.
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W.L.Dong,
Y.Q.Ge,
and
B.X.Zhao
(2007).
Ethyl 5-(ethoxy-carbon-yl)-3-(4-methoxy-phen-yl)-1H-pyrazole-1-acetate.
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Acta Crystallogr Sect E Struct Rep Online,
64,
o64.
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P.Workman
(2005).
Drugging the cancer kinome: progress and challenges in developing personalized molecular cancer therapeutics.
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Cold Spring Harb Symp Quant Biol,
70,
499-515.
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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
codes are
shown on the right.
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Links
