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PDBsum entry 2p5b
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Metal binding protein
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PDB id
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2p5b
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References listed in PDB file
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Key reference
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Title
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Structural basis of the recognition of a methylated histone tail by jmjd2a.
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Authors
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Z.Chen,
J.Zang,
J.Kappler,
X.Hong,
F.Crawford,
Q.Wang,
F.Lan,
C.Jiang,
J.Whetstine,
S.Dai,
K.Hansen,
Y.Shi,
G.Zhang.
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Ref.
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Proc Natl Acad Sci U S A, 2007,
104,
10818-10823.
[DOI no: ]
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PubMed id
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Abstract
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The Jumonji C domain is a catalytic motif that mediates histone lysine
demethylation. The Jumonji C-containing oxygenase JMJD2A specifically
demethylates tri- and dimethylated lysine-9 and lysine-36 of histone 3 (H3K9/36
me3/2). Here we present structures of the JMJD2A catalytic core complexed with
methylated H3K36 peptide substrates in the presence of Fe(II) and
N-oxalylglycine. We found that the interaction between JMJD2A and peptides
largely involves the main chains of the enzyme and the peptide. The
peptide-binding specificity is primarily determined by the primary structure of
the peptide, which explains the specificity of JMJD2A for methylated H3K9 and
H3K36 instead of other methylated residues such as H3K27. The specificity for a
particular methyl group, however, is affected by multiple factors, such as space
and the electrostatic environment in the catalytic center of the enzyme. These
results provide insights into the mechanisms and specificity of histone
demethylation.
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Figure 1.
Fig. 1. The overall complex structure of c-JMJD2A with the
H3K36me3 peptide in the presence of NOG (orange), Fe(II) (pink),
and Zn (purple). (A) c-JMJD2A is shown as a ribbon model with
the Jumonji N domain (green), the long  hairpin (purple), the
mixed structural motif (gray), the Jumonji C domain (light
blue), the C-terminal domain (pink), and the methylated H3K36
peptide (yellow). Seventeen of the 22 residues (residues 27–43
from histone 3) of the methylated peptide are ordered in the
structure (molecule A). (B) A stick and ball model of the
peptide on the surface of c-JMJD2A colored according to the
electrostatic potential of the residues (red and blue represent
negatively and positively charged areas, respectively). All
structural figures were made by using the PyMOL program
(http://pymol.sourceforge.net).
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Figure 2.
Fig. 2. The detailed interaction between c-JMJD2A and the
methylated peptides. (A) A schematic view of all of the
potential interactions between c-JMJD2A and the H3K36 peptide,
including 10 hydrogen bonds and one salt bridge. (B) Mutagenesis
data and activity assays. Residues Q86, N88, D135, and Y175 are
involved in the interaction with the peptide, whereas residues
Y177, N290, S288, and T289 are involved in methyl group binding.
K241 is proposed to recruit the O[2] molecule into the catalytic
center. (C) Characterization of the binding between the H3K36
peptide and c-JMJD2A. (D) Characterization of the binding
between of the H3K9 peptide and c-JMJD2A. Neither of the binding
curves is linear, suggesting that the peptides assume multiple
conformations.
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