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Chembiochem. 2015 Jan 2;16(1):119-25. doi: 10.1002/cbic.201402522. Epub 2014 Nov 17.

Ergothioneine biosynthetic methyltransferase EgtD reveals the structural basis of aromatic amino acid betaine biosynthesis.

Author information

  • 13Structure 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).

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.

KEYWORDS:

amino acids; betaines; biosynthesis; ergothioneine; hypaphorine; methyltransferases

PMID:
25404173
DOI:
10.1002/cbic.201402522
[PubMed - indexed for MEDLINE]
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