2Y48

Crystal structure of LSD1-CoREST in complex with a N-terminal SNAIL peptide

Summary for 2Y48

• Entry DOI: 10.2210/pdb2y48/pdb
• Related: 2COM 2H94 2IW5 2UXN 2UXX 2V1D 2X0L 2XAF 2XAG 2XAH 2XAJ 2XAQ 2XAS
• Descriptor: LYSINE-SPECIFIC DEMETHYLASE 1A, REST COREPRESSOR 1, ZINC FINGER PROTEIN SNAI1, ... (4 entities in total)
• Functional Keywords: oxidoreductase, flavin, histone, repressor, transcription regulation, chromatin, nuclear protein
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus: O60341 Q9UKL0 O95863
• Total number of polymer chains: 3
• Total formula weight: 104702.50

Authors

Baron, R.,Binda, C.,Tortorici, M.,McCammon, J.A.,Mattevi, A. (deposition date: 2011-01-05, release date: 2011-02-16, Last modification date: 2023-12-20)

Primary citation

Baron, R.,Binda, C.,Tortorici, M.,Mccammon, J.A.,Mattevi, A.
Molecular Mimicry and Ligand Recognition in Binding and Catalysis by the Histone Demethylase Lsd1-Corest Complex.
Structure, 19:212-, 2011

PubMed Abstract: Histone demethylases LSD1 and LSD2 (KDM1A/B) catalyze the oxidative demethylation of Lys4 of histone H3. We used molecular dynamics simulations to probe the diffusion of the oxygen substrate. Oxygen can reach the catalytic center independently from the presence of a bound histone peptide, implying that LSD1 can complete subsequent demethylation cycles without detaching from the nucleosomal particle. The simulations highlight the role of a strictly conserved active-site Lys residue providing general insight into the enzymatic mechanism of oxygen-reacting flavoenzymes. The crystal structure of LSD1-CoREST bound to a peptide of the transcription factor SNAIL1 unravels a fascinating example of molecular mimicry. The SNAIL1 N-terminal residues bind to the enzyme active-site cleft, effectively mimicking the H3 tail. This finding predicts that other members of the SNAIL/Scratch transcription factor family might associate to LSD1/2. The combination of selective histone-modifying activity with the distinct recognition mechanisms underlies the biological complexity of LSD1/2.

PubMed: 21300290
DOI: 10.1016/J.STR.2011.01.001

Experimental method

X-RAY DIFFRACTION (3 Å)