2v1d
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Histone demethylase LSD1 regulates transcription by demethylating Lys(4) | + | Histone demethylase LSD1 regulates transcription by demethylating Lys(4) of histone H3. The crystal structure of the enzyme in complex with CoREST and a substrate-like peptide inhibitor highlights an intricate network of interactions and a folded conformation of the bound peptide. The core of the peptide structure is formed by Arg(2), Gln(5), and Ser(10), which are engaged in specific intramolecular H-bonds. Several charged side chains on the surface of the substrate-binding pocket establish electrostatic interactions with the peptide. The three-dimensional structure predicts that methylated Lys(4) binds in a solvent inaccessible position in front of the flavin cofactor. This geometry is fully consistent with the demethylation reaction being catalyzed through a flavin-mediated oxidation of the substrate amino-methyl group. These features dictate the exquisite substrate specificity of LSD1 and provide a structural framework to explain the fine tuning of its catalytic activity and the active role of CoREST in substrate recognition. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Structural | + | Structural basis of LSD1-CoREST selectivity in histone H3 recognition., Forneris F, Binda C, Adamo A, Battaglioli E, Mattevi A, J Biol Chem. 2007 Jul 13;282(28):20070-4. Epub 2007 May 30. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17537733 17537733] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: transcription regulation]] | [[Category: transcription regulation]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:52:25 2008'' |
Revision as of 16:52, 21 February 2008
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STRUCTURAL BASIS OF LSD1-COREST SELECTIVITY IN HISTONE H3 RECOGNITION
Overview
Histone demethylase LSD1 regulates transcription by demethylating Lys(4) of histone H3. The crystal structure of the enzyme in complex with CoREST and a substrate-like peptide inhibitor highlights an intricate network of interactions and a folded conformation of the bound peptide. The core of the peptide structure is formed by Arg(2), Gln(5), and Ser(10), which are engaged in specific intramolecular H-bonds. Several charged side chains on the surface of the substrate-binding pocket establish electrostatic interactions with the peptide. The three-dimensional structure predicts that methylated Lys(4) binds in a solvent inaccessible position in front of the flavin cofactor. This geometry is fully consistent with the demethylation reaction being catalyzed through a flavin-mediated oxidation of the substrate amino-methyl group. These features dictate the exquisite substrate specificity of LSD1 and provide a structural framework to explain the fine tuning of its catalytic activity and the active role of CoREST in substrate recognition.
About this Structure
2V1D is a Protein complex structure of sequences from Homo sapiens with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Structural basis of LSD1-CoREST selectivity in histone H3 recognition., Forneris F, Binda C, Adamo A, Battaglioli E, Mattevi A, J Biol Chem. 2007 Jul 13;282(28):20070-4. Epub 2007 May 30. PMID:17537733
Page seeded by OCA on Thu Feb 21 18:52:25 2008
Categories: Homo sapiens | Protein complex | Adamo, A. | Battaglioli, E. | Binda, C. | Forneris, F. | Mattevi, A. | FAD | Alternative splicing | Amine oxidase | Chromatin regulator | Coiled coil | Fad | Flavin | Histone demethylase | Host-virus interaction | Lsd1 | Nuclear protein | Oxidoreductase | Oxidoreductase/repressor complex chromatin remodelling | Phosphorylation | Repressor | Transcription | Transcription regulation
