2h94
From Proteopedia
(New page: 200px<br /> <applet load="2h94" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h94, resolution 2.900Å" /> '''Crystal Structure ...) |
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caption="2h94, resolution 2.900Å" /> | caption="2h94, resolution 2.900Å" /> | ||
'''Crystal Structure and Mechanism of human Lysine-Specific Demethylase-1'''<br /> | '''Crystal Structure and Mechanism of human Lysine-Specific Demethylase-1'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The reversible methylation of specific lysine residues in histone tails is | + | The reversible methylation of specific lysine residues in histone tails is crucial in epigenetic gene regulation. LSD1, the first known lysine-specific demethylase, selectively removes monomethyl and dimethyl, but not trimethyl modifications of Lys4 or Lys9 of histone-3. Here, we present the crystal structure of LSD1 at 2.9-A resolution. LSD1 forms a highly asymmetric, closely packed domain structure from which a long helical 'tower' domain protrudes. The active site cavity is spacious enough to accommodate several residues of the histone tail substrate, but does not appear capable of recognizing the different methylation states of the substrate lysine. This supports the hypothesis that trimethylated lysine is chemically rather than sterically discriminated. We present a biochemical analysis of LSD1 mutants that identifies crucial residues in the active site cavity and shows the importance of the SWIRM and tower domains for catalysis. |
==About this Structure== | ==About this Structure== | ||
| - | 2H94 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 HG and FAD as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2H94 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=HG:'>HG</scene> and <scene name='pdbligand=FAD:'>FAD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H94 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: histone demethylase]] | [[Category: histone demethylase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:39:26 2008'' |
Revision as of 15:39, 21 February 2008
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Crystal Structure and Mechanism of human Lysine-Specific Demethylase-1
Overview
The reversible methylation of specific lysine residues in histone tails is crucial in epigenetic gene regulation. LSD1, the first known lysine-specific demethylase, selectively removes monomethyl and dimethyl, but not trimethyl modifications of Lys4 or Lys9 of histone-3. Here, we present the crystal structure of LSD1 at 2.9-A resolution. LSD1 forms a highly asymmetric, closely packed domain structure from which a long helical 'tower' domain protrudes. The active site cavity is spacious enough to accommodate several residues of the histone tail substrate, but does not appear capable of recognizing the different methylation states of the substrate lysine. This supports the hypothesis that trimethylated lysine is chemically rather than sterically discriminated. We present a biochemical analysis of LSD1 mutants that identifies crucial residues in the active site cavity and shows the importance of the SWIRM and tower domains for catalysis.
About this Structure
2H94 is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure and mechanism of human lysine-specific demethylase-1., Stavropoulos P, Blobel G, Hoelz A, Nat Struct Mol Biol. 2006 Jul;13(7):626-32. Epub 2006 Jun 25. PMID:16799558
Page seeded by OCA on Thu Feb 21 17:39:26 2008
