2W5Z

Ternary Complex of the Mixed Lineage Leukaemia (MLL1) SET Domain with the cofactor product S-Adenosylhomocysteine and histone peptide.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.197 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structural Basis for the Requirement of Additional Factors for Mll1 Set Domain Activity and Recognition of Epigenetic Marks.

Southall, S.M.Wong, P.S.Odho, Z.Roe, S.M.Wilson, J.R.

(2009) Mol Cell 33: 181

  • DOI: https://doi.org/10.1016/j.molcel.2008.12.029
  • Primary Citation of Related Structures:  
    2W5Y, 2W5Z

  • PubMed Abstract: 

    The mixed-lineage leukemia protein MLL1 is a transcriptional regulator with an essential role in early development and hematopoiesis. The biological function of MLL1 is mediated by the histone H3K4 methyltransferase activity of the carboxyl-terminal SET domain. We have determined the crystal structure of the MLL1 SET domain in complex with cofactor product AdoHcy and a histone H3 peptide. This structure indicates that, in order to form a well-ordered active site, a highly variable but essential component of the SET domain must be repositioned. To test this idea, we compared the effect of the addition of MLL complex members on methyltransferase activity and show that both RbBP5 and Ash2L but not Wdr5 stimulate activity. Additionally, we have determined the effect of posttranslational modifications on histone H3 residues downstream and upstream from the target lysine and provide a structural explanation for why H3T3 phosphorylation and H3K9 acetylation regulate activity.


  • Organizational Affiliation

    Institute of Cancer Research, Chester Beatty Laboratories, Chelsea, London, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HISTONE-LYSINE N-METHYLTRANSFERASE HRX192Homo sapiensMutation(s): 0 
EC: 2.1.1.43
UniProt & NIH Common Fund Data Resources
Find proteins for Q03164 (Homo sapiens)
Explore Q03164 
Go to UniProtKB:  Q03164
PHAROS:  Q03164
GTEx:  ENSG00000118058 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ03164
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
HISTONE PEPTIDEB [auth C]9Homo sapiensMutation(s): 0 
EC: 2.1.1.43
UniProt
Find proteins for P68433 (Mus musculus)
Explore P68433 
Go to UniProtKB:  P68433
Entity Groups  
UniProt GroupP68433
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MLY
Query on MLY
B [auth C]L-PEPTIDE LINKINGC8 H18 N2 O2LYS
Binding Affinity Annotations 
IDSourceBinding Affinity
SAH BindingDB:  2W5Z IC50: 2300 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.197 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.95α = 90
b = 56.55β = 90
c = 78.41γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
MOSFLMdata reduction
SCALEPACKdata scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-02-10
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance