Ergothioneine Biosynthetic Methyltransferase EgtD Reveals the Structural Basis of Aromatic Amino Acid Betaine Biosynthesis. Issue 1 (17th November 2014)

• Record Type: Journal Article
• Authors: Vit, Allegra; Misson, Laëtitia; Blankenfeldt, Wulf; Seebeck, Florian P.
• Is Part Of: Chembiochem. Volume 16:Issue 1(2015)
• Page Start: 119
• Page End: 125
• Publication Date: 2014-11-17
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201402522
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Ergothioneine is an <italic>N</italic>‐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 <italic>N</italic>‐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 10⁷‐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.</p> </abstract>