4PIO

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

Summary for 4PIO

• Entry DOI: 10.2210/pdb4pio/pdb
• Related: 4PIM 4PIN 4PIP
• Descriptor: Histidine-specific methyltransferase EgtD, S-ADENOSYL-L-HOMOCYSTEINE, N,N-dimethyl-L-histidine, ... (6 entities in total)
• Functional Keywords: methyltransferase, ergothioneine, histidine betaine, transferase
• Biological source: Mycobacterium smegmatis
• Total number of polymer chains: 2
• Total formula weight: 71945.91

Authors

Vit, A.,Seebeck, F.P.,Blankenfeldt, W. (deposition date: 2014-05-09, release date: 2014-12-03, Last modification date: 2023-09-27)

Primary citation

Vit, A.,Misson, L.,Blankenfeldt, W.,Seebeck, F.P.
Ergothioneine Biosynthetic Methyltransferase EgtD Reveals the Structural Basis of Aromatic Amino Acid Betaine Biosynthesis.
Chembiochem, 16:119-125, 2015

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.

PubMed: 25404173
DOI: 10.1002/cbic.201402522

Experimental method

X-RAY DIFFRACTION (1.506 Å)