2V1D

Structural basis of LSD1-CoREST selectivity in histone H3 recognition


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.10 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.224 

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Literature

Structural Basis of Lsd1-Corest Selectivity in Histone H3 Recognition.

Forneris, F.Binda, C.Adamo, A.Battaglioli, E.Mattevi, A.

(2007) J Biol Chem 282: 20070

  • DOI: https://doi.org/10.1074/jbc.C700100200
  • Primary Citation of Related Structures:  
    2V1D

  • 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.


  • Organizational Affiliation

    Dipartimento di Genetica e Microbiologia, Università di Pavia, Via Ferrata 1, 27100 Pavia, Italy.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
LYSINE-SPECIFIC HISTONE DEMETHYLASE 1730Homo sapiensMutation(s): 0 
EC: 1
UniProt & NIH Common Fund Data Resources
Find proteins for O60341 (Homo sapiens)
Explore O60341 
Go to UniProtKB:  O60341
PHAROS:  O60341
GTEx:  ENSG00000004487 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO60341
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
REST COREPRESSOR 1178Homo sapiensMutation(s): 0 
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Find proteins for Q9UKL0 (Homo sapiens)
Explore Q9UKL0 
Go to UniProtKB:  Q9UKL0
PHAROS:  Q9UKL0
GTEx:  ENSG00000089902 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UKL0
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
HISTONE H3.1T21Homo sapiensMutation(s): 1 
UniProt & NIH Common Fund Data Resources
Find proteins for Q16695 (Homo sapiens)
Explore Q16695 
Go to UniProtKB:  Q16695
PHAROS:  Q16695
GTEx:  ENSG00000168148 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ16695
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FAD
Query on FAD

Download Ideal Coordinates CCD File 
D [auth A]FLAVIN-ADENINE DINUCLEOTIDE
C27 H33 N9 O15 P2
VWWQXMAJTJZDQX-UYBVJOGSSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.10 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.224 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 120.057α = 90
b = 180.496β = 90
c = 233.387γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-05-29
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description