5HT6

Crystal structure of the SET domain of the human MLL5 methyltransferase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.09 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.212 

wwPDB Validation   3D Report Full Report


This is version 1.0 of the entry. See complete history


Literature

The Human Mixed Lineage Leukemia 5 (MLL5), a Sequentially and Structurally Divergent SET Domain-Containing Protein with No Intrinsic Catalytic Activity.

Mas-Y-Mas, S.Barbon, M.Teyssier, C.Demene, H.Carvalho, J.E.Bird, L.E.Lebedev, A.Fattori, J.Schubert, M.Dumas, C.Bourguet, W.le Maire, A.

(2016) PLoS One 11: e0165139-e0165139

  • DOI: https://doi.org/10.1371/journal.pone.0165139
  • Primary Citation of Related Structures:  
    5HT6

  • PubMed Abstract: 

    Mixed Lineage Leukemia 5 (MLL5) plays a key role in hematopoiesis, spermatogenesis and cell cycle progression. Chromatin binding is ensured by its plant homeodomain (PHD) through a direct interaction with the N-terminus of histone H3 (H3). In addition, MLL5 contains a Su(var)3-9, Enhancer of zeste, Trithorax (SET) domain, a protein module that usually displays histone lysine methyltransferase activity. We report here the crystal structure of the unliganded SET domain of human MLL5 at 2.1 Å resolution. Although it shows most of the canonical features of other SET domains, both the lack of key residues and the presence in the SET-I subdomain of an unusually large loop preclude the interaction of MLL5 SET with its cofactor and substrate. Accordingly, we show that MLL5 is devoid of any in vitro methyltransferase activity on full-length histones and histone H3 peptides. Hence, the three dimensional structure of MLL5 SET domain unveils the structural basis for its lack of methyltransferase activity and suggests a new regulatory mechanism.


  • Organizational Affiliation

    Inserm U1054, Centre de Biochimie Structurale, Montpellier, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Histone-lysine N-methyltransferase 2E
A, B
138Homo sapiensMutation(s): 1 
Gene Names: KMT2EMLL5
EC: 2.1.1.43
UniProt & NIH Common Fund Data Resources
Find proteins for Q8IZD2 (Homo sapiens)
Explore Q8IZD2 
Go to UniProtKB:  Q8IZD2
PHAROS:  Q8IZD2
GTEx:  ENSG00000005483 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8IZD2
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.09 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.212 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.9α = 90
b = 65.9β = 90
c = 112.9γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
SCALAdata scaling
PDB_EXTRACTdata extraction
XDSdata reduction
PHASERphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Assocation pour la Recherche contre le CancerFrance075427

Revision History  (Full details and data files)

  • Version 1.0: 2016-11-16
    Type: Initial release