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PDBsum entry 4ai9
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Oxidoreductase
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PDB id
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4ai9
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References listed in PDB file
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Key reference
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Title
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Plant growth regulator daminozide is a selective inhibitor of human kdm2/7 histone demethylases.
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Authors
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N.R.Rose,
E.C.Woon,
A.Tumber,
L.J.Walport,
R.Chowdhury,
X.S.Li,
O.N.King,
C.Lejeune,
S.S.Ng,
T.Krojer,
M.C.Chan,
A.M.Rydzik,
R.J.Hopkinson,
K.H.Che,
M.Daniel,
C.Strain-Damerell,
C.Gileadi,
G.Kochan,
I.K.Leung,
J.Dunford,
K.K.Yeoh,
P.J.Ratcliffe,
N.Burgess-Brown,
F.Von delft,
S.Muller,
B.Marsden,
P.E.Brennan,
M.A.Mcdonough,
U.Oppermann,
R.J.Klose,
C.J.Schofield,
A.Kawamura.
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Ref.
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J Med Chem, 2012,
55,
6639-6643.
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PubMed id
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Abstract
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The JmjC oxygenases catalyze the N-demethylation of N(ε)-methyl lysine residues
in histones and are current therapeutic targets. A set of human 2-oxoglutarate
analogues were screened using a unified assay platform for JmjC demethylases and
related oxygenases. Results led to the finding that daminozide
(N-(dimethylamino)succinamic acid, 160 Da), a plant growth regulator,
selectively inhibits the KDM2/7 JmjC subfamily. Kinetic and crystallographic
studies reveal that daminozide chelates the active site metal via its hydrazide
carbonyl and dimethylamino groups.
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