3ZMU

LSD1-CoREST in complex with PKSFLV peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Protein Recognition by Small Peptide Reversible Inhibitors of the Chromatin-Modifying Lsd1/Corest Lysine Demethylase.

Tortorici, M.Borrello, M.T.Tardugno, M.Chiarelli, L.R.Pilotto, S.Ciossani, G.Vellore, N.A.Bailey, S.G.Cowan, J.O'Connell, M.Crabb, S.J.Packham, G.K.Mai, A.Baron, R.Ganesan, A.Mattevi, A.

(2013) ACS Chem Biol 8: 1677-1682

  • DOI: https://doi.org/10.1021/cb4001926
  • Primary Citation of Related Structures:  
    3ZMS, 3ZMT, 3ZMU, 3ZMV, 3ZMZ, 3ZN0, 3ZN1

  • PubMed Abstract: 

    The combinatorial assembly of protein complexes is at the heart of chromatin biology. Lysine demethylase LSD1(KDM1A)/CoREST beautifully exemplifies this concept. The active site of the enzyme tightly associates to the N-terminal domain of transcription factors of the SNAIL1 family, which therefore can competitively inhibit the binding of the N-terminal tail of the histone substrate. Our enzymatic, crystallographic, spectroscopic, and computational studies reveal that LSD1/CoREST can bind to a hexapeptide derived from the SNAIL sequence through recognition of a positively charged α-helical turn that forms upon binding to the enzyme. Variations in sequence and length of this six amino acid ligand modulate affinities enabling the same binding site to differentially interact with proteins that exert distinct biological functions. The discovered short peptide inhibitors exhibit antiproliferative activities and lay the foundation for the development of peptidomimetic small molecule inhibitors of LSD1.


  • Organizational Affiliation

    Department of Biology and Biotechnology, University of Pavia, via Ferrata 9, 27100 Pavia, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
LYSINE-SPECIFIC HISTONE DEMETHYLASE 1A872Homo 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 1482Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
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
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
PKSFLV PEPTIDE6Homo sapiensMutation(s): 0 
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: 3.20 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.206 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 120.1α = 90
b = 180.17β = 90
c = 233.958γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2013-06-12
    Type: Initial release
  • Version 1.1: 2013-08-28
    Changes: Database references
  • Version 1.2: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description