2v1d

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spinqualitylabelsall models 2v1d, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 FAD as ligand. Structure known Active Site: AC1. 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 Mon Nov 12 23:41:36 2007