4HOO

Crystal structure of human JMJD2D/KDM4D apoenzyme


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural and Functional Analysis of JMJD2D Reveals Molecular Basis for Site-Specific Demethylation among JMJD2 Demethylases.

Krishnan, S.Trievel, R.C.

(2013) Structure 21: 98-108

  • DOI: https://doi.org/10.1016/j.str.2012.10.018
  • Primary Citation of Related Structures:  
    4HON, 4HOO

  • PubMed Abstract: 

    JMJD2 lysine demethylases (KDMs) participate in diverse genomic processes. Most JMJD2 homologs display dual selectivity toward H3K9me3 and H3K36me3, with the exception of JMJD2D, which is specific for H3K9me3. Here, we report the crystal structures of the JMJD2D⋅2-oxoglutarate⋅H3K9me3 ternary complex and JMJD2D apoenzyme. Utilizing structural alignments with JMJD2A, molecular docking, and kinetic analysis with an array of histone peptide substrates, we elucidate the specific signatures that permit efficient recognition of H3K9me3 by JMJD2A and JMJD2D, and the residues in JMJD2D that occlude H3K36me3 demethylation. Surprisingly, these results reveal that JMJD2A and JMJD2D exhibit subtle yet important differences in H3K9me3 recognition, despite the overall similarity in the substrate-binding conformation. Further, we show that H3T11 phosphorylation abrogates demethylation by JMJD2 KDMs. Together, these studies reveal the molecular basis for JMJD2 site specificity and provide a framework for structure-based design of selective inhibitors of JMJD2 KDMs implicated in disease.


  • Organizational Affiliation

    Department of Biological Chemistry, 1150 West Medical Center Drive, 5301 Medical Science Research Building III, University of Michigan, Ann Arbor, MI 48109, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Lysine-specific demethylase 4D
A, B
330Homo sapiensMutation(s): 2 
Gene Names: JHDM3DJMJD2DKDM4D
EC: 1.14.11
UniProt & NIH Common Fund Data Resources
Find proteins for Q6B0I6 (Homo sapiens)
Explore Q6B0I6 
Go to UniProtKB:  Q6B0I6
PHAROS:  Q6B0I6
GTEx:  ENSG00000186280 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6B0I6
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 
  • Space Group: P 32
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 73.119α = 90
b = 73.119β = 90
c = 136.028γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection
HKL-2000data reduction
CCP4phasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-11-21
    Type: Initial release
  • Version 1.1: 2013-01-02
    Changes: Database references
  • Version 1.2: 2013-01-30
    Changes: Database references
  • Version 1.3: 2017-11-15
    Changes: Refinement description
  • Version 1.4: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description