4PIN

Ergothioneine-biosynthetic methyltransferase EgtD in complex with N,N-dimethylhistidine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.200 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Ergothioneine Biosynthetic Methyltransferase EgtD Reveals the Structural Basis of Aromatic Amino Acid Betaine Biosynthesis.

Vit, A.Misson, L.Blankenfeldt, W.Seebeck, F.P.

(2015) Chembiochem 16: 119-125

  • DOI: https://doi.org/10.1002/cbic.201402522
  • Primary Citation of Related Structures:  
    4PIM, 4PIN, 4PIO, 4PIP

  • PubMed Abstract: 

    Ergothioneine is an N-α-trimethyl-2-thiohistidine derivative that occurs in human, plant, fungal, and bacterial cells. Biosynthesis of this redox-active betaine starts with trimethylation of the α-amino group of histidine. The three consecutive methyl transfers are catalyzed by the S-adenosylmethionine-dependent methyltransferase EgtD. Three crystal structures of this enzyme in the absence and in the presence of N-α-dimethylhistidine and S-adenosylhomocysteine implicate a preorganized array of hydrophilic interactions as the determinants for substrate specificity and apparent processivity. We identified two active site mutations that change the substrate specificity of EgtD 10(7)-fold and transform the histidine-methyltransferase into a proficient tryptophan-methyltransferase. Finally, a genomic search for EgtD homologues in fungal genomes revealed tyrosine and tryptophan trimethylation activity as a frequent trait in ascomycetous and basidomycetous fungi.


  • Organizational Affiliation

    3Structure and Function of Proteins, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig (Germany); Previous address: Department of Biochemistry, University of Bayreuth, Universitätsstrasse 30, 95447 Bayreuth (Germany).


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Histidine-specific methyltransferase EgtD
A, B
323Mycolicibacterium smegmatisMutation(s): 4 
Gene Names: egtDMSMEG_6247MSMEI_6086
EC: 2.1.1.44
UniProt
Find proteins for A0R5M8 (Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155))
Explore A0R5M8 
Go to UniProtKB:  A0R5M8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0R5M8
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.200 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.988α = 90
b = 74.757β = 90
c = 137.812γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
XDSdata scaling
PDB_EXTRACTdata extraction
PHENIXrefinement
REFMACphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Swiss National FoundationSwitzerland147005

Revision History  (Full details and data files)

  • Version 1.0: 2014-12-03
    Type: Initial release
  • Version 1.1: 2015-01-07
    Changes: Database references
  • Version 1.2: 2017-11-22
    Changes: Advisory, Derived calculations, Other, Refinement description, Source and taxonomy
  • Version 1.3: 2023-09-27
    Changes: Data collection, Database references, Refinement description