2h94
From Proteopedia
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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 HG and FAD 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
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