2V1D

Structural basis of LSD1-CoREST selectivity in histone H3 recognition

Summary for 2V1D

• Entry DOI: 10.2210/pdb2v1d/pdb
• Related: 2COM 2H94 2IW5 2UXN 2UXX 2X0L
• Descriptor: LYSINE-SPECIFIC HISTONE DEMETHYLASE 1, REST COREPRESSOR 1, HISTONE H3.1T, ... (4 entities in total)
• Functional Keywords: oxidoreductase repressor complex, alternative splicing, oxidoreductase, flavin, repressor, transcription regulation, chromatin remodelling, host-virus interaction, nuclear protein, phosphorylation, chromatin regulator, oxidoreductase-repressor complex, oxidoreductase/repressor
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus: O60341 Q9UKL0 Q16695
• Total number of polymer chains: 3
• Total formula weight: 104573.48

Authors

Forneris, F.,Binda, C.,Adamo, A.,Battaglioli, E.,Mattevi, A. (deposition date: 2007-05-23, release date: 2007-05-29, Last modification date: 2023-12-13)

Primary citation

Forneris, F.,Binda, C.,Adamo, A.,Battaglioli, E.,Mattevi, A.
Structural Basis of Lsd1-Corest Selectivity in Histone H3 Recognition.
J.Biol.Chem., 282:20070-, 2007

PubMed Abstract: 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.

PubMed: 17537733
DOI: 10.1074/JBC.C700100200

Experimental method

X-RAY DIFFRACTION (3.1 Å)