2q8c: Difference between revisions
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caption="2q8c, resolution 2.047Å" /> | caption="2q8c, resolution 2.047Å" /> | ||
'''Crystal structure of JMJD2A in ternary complex with an histone H3K9me3 peptide and 2-oxoglutarate'''<br /> | '''Crystal structure of JMJD2A in ternary complex with an histone H3K9me3 peptide and 2-oxoglutarate'''<br /> | ||
==Overview== | |||
JMJD2A is a JmjC histone demethylase (HDM) that catalyzes the, demethylation of di- and trimethylated Lys9 and Lys36 in histone H3, (H3K9me2/3 and H3K36me2/3). Here we present the crystal structures of the, JMJD2A catalytic domain in complex with H3K9me3, H3K36me2 and H3K36me3, peptides. The structures reveal that histone substrates are recognized, through a network of backbone hydrogen bonds and hydrophobic interactions, that deposit the trimethyllysine into the active site. The trimethylated, epsilon-ammonium cation is coordinated within a methylammonium-binding, pocket through carbon-oxygen (CH...O) hydrogen bonds that position one of, the zeta-methyl groups adjacent to the Fe(II) center for hydroxylation and, demethylation. Mutations of the residues comprising this pocket abrogate, demethylation by JMJD2A, with the exception of an S288A substitution, which augments activity, particularly toward H3K9me2. We propose that this, residue modulates the methylation-state specificities of JMJD2 enzymes and, other trimethyllysine-specific JmjC HDMs. | |||
==About this Structure== | ==About this Structure== | ||
2Q8C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NI:'>NI</scene>, <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=AKG:'>AKG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q8C OCA]. | 2Q8C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NI:'>NI</scene>, <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=AKG:'>AKG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q8C OCA]. | ||
==Reference== | |||
Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase., Couture JF, Collazo E, Ortiz-Tello PA, Brunzelle JS, Trievel RC, Nat Struct Mol Biol. 2007 Aug;14(8):689-95. Epub 2007 Jun 24. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17589523 17589523] | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: jumonji]] | [[Category: jumonji]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jan 31 10:58:13 2008'' | ||
Revision as of 11:58, 31 January 2008
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Crystal structure of JMJD2A in ternary complex with an histone H3K9me3 peptide and 2-oxoglutarate
OverviewOverview
JMJD2A is a JmjC histone demethylase (HDM) that catalyzes the, demethylation of di- and trimethylated Lys9 and Lys36 in histone H3, (H3K9me2/3 and H3K36me2/3). Here we present the crystal structures of the, JMJD2A catalytic domain in complex with H3K9me3, H3K36me2 and H3K36me3, peptides. The structures reveal that histone substrates are recognized, through a network of backbone hydrogen bonds and hydrophobic interactions, that deposit the trimethyllysine into the active site. The trimethylated, epsilon-ammonium cation is coordinated within a methylammonium-binding, pocket through carbon-oxygen (CH...O) hydrogen bonds that position one of, the zeta-methyl groups adjacent to the Fe(II) center for hydroxylation and, demethylation. Mutations of the residues comprising this pocket abrogate, demethylation by JMJD2A, with the exception of an S288A substitution, which augments activity, particularly toward H3K9me2. We propose that this, residue modulates the methylation-state specificities of JMJD2 enzymes and, other trimethyllysine-specific JmjC HDMs.
About this StructureAbout this Structure
2Q8C is a Single protein structure of sequence from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase., Couture JF, Collazo E, Ortiz-Tello PA, Brunzelle JS, Trievel RC, Nat Struct Mol Biol. 2007 Aug;14(8):689-95. Epub 2007 Jun 24. PMID:17589523
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