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PDBsum entry 3e63
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Contents |
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* Residue conservation analysis
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PDB id:
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Transferase
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Title:
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Fragment based discovery of jak-2 inhibitors
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Structure:
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Tyrosine-protein kinase jak2. Chain: a. Fragment: catalytic domain (unp residues 839 to 1131). Synonym: janus kinase 2, jak-2. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: jak2. Expressed in: unidentified baculovirus. Expression_system_taxid: 10469.
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Resolution:
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1.90Å
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R-factor:
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0.203
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R-free:
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0.263
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Authors:
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S.Antonysamy,W.Fang,G.Hirst,F.Park,M.Russell,L.Smyth,P.Sprengeler, F.Stappenbeck,R.Steensma,D.A.Thompson,M.Wilson,M.Wong,A.Zhang, F.Zhang
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Key ref:
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S.Antonysamy
et al.
(2009).
Fragment-based discovery of JAK-2 inhibitors.
Bioorg Med Chem Lett,
19,
279-282.
PubMed id:
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Date:
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14-Aug-08
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Release date:
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14-Oct-08
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PROCHECK
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Headers
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References
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O60674
(JAK2_HUMAN) -
Tyrosine-protein kinase JAK2 from Homo sapiens
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Seq:
Struc:
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1132 a.a.
292 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.2.7.10.2
- non-specific protein-tyrosine kinase.
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Reaction:
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L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
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L-tyrosyl-[protein]
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+
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ATP
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=
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O-phospho-L-tyrosyl-[protein]
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+
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ADP
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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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Bioorg Med Chem Lett
19:279-282
(2009)
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PubMed id:
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Fragment-based discovery of JAK-2 inhibitors.
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S.Antonysamy,
G.Hirst,
F.Park,
P.Sprengeler,
F.Stappenbeck,
R.Steensma,
M.Wilson,
M.Wong.
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ABSTRACT
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Fragment-based hit identification coupled with crystallographically enabled
structure-based drug design was used to design potent inhibitors of JAK-2. After
two iterations from fragment 1, we were able to increase potency by greater than
500-fold to provide sulfonamide 13, a 78-nM JAK-2 inhibitor.
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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.G.Coyne,
D.E.Scott,
and
C.Abell
(2010).
Drugging challenging targets using fragment-based approaches.
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Curr Opin Chem Biol,
14,
299-307.
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C.W.Murray,
and
T.L.Blundell
(2010).
Structural biology in fragment-based drug design.
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Curr Opin Struct Biol,
20,
497-507.
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T.Okuzumi,
G.S.Ducker,
C.Zhang,
B.Aizenstein,
R.Hoffman,
and
K.M.Shokat
(2010).
Synthesis and evaluation of indazole based analog sensitive Akt inhibitors.
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Mol Biosyst,
6,
1389-1402.
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Y.Hitoshi,
N.Lin,
D.G.Payan,
and
V.Markovtsov
(2010).
The current status and the future of JAK2 inhibitors for the treatment of myeloproliferative diseases.
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Int J Hematol,
91,
189-200.
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R.Kiss,
T.Polgár,
A.Kirabo,
J.Sayyah,
N.C.Figueroa,
A.F.List,
L.Sokol,
K.S.Zuckerman,
M.Gali,
K.S.Bisht,
P.P.Sayeski,
and
G.M.Keseru
(2009).
Identification of a novel inhibitor of JAK2 tyrosine kinase by structure-based virtual screening.
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Bioorg Med Chem Lett,
19,
3598-3601.
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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.
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Links
