Premium
Structures in Tetrahydrofolate Methylation in Desulfitobacterial Glycine Betaine Metabolism at Atomic Resolution
Author(s) -
Badmann Thomas,
Groll Michael
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900515
Subject(s) - chemistry , methylation , moiety , stereochemistry , betaine , methyltransferase , transmethylation , methyl group , methanethiol , biochemistry , sulfur , dna , organic chemistry , alkyl
Enzymes orchestrating methylation between tetrahydrofolate (THF) and cobalamin (Cbl) are abundant among all domains of life. During energy production in Desulfitobacterium hafniense , MtgA catalyzes the methyl transfer from methylcobalamin (Cbl‐CH 3 ) to THF in the catabolism of glycine betaine (GB). Despite its lack of sequence identity with known structures, we could show that MtgA forms a homodimeric complex of two TIM barrels. Atomic crystallographic insights into the interplay of MtgA with THF as well as analysis of a trapped reaction intermediate (THF‐CH 3 ) + reveal conformational rearrangements during the transfer reaction. Whereas residues for THF methylation are conserved, the binding mode for the THF glutamyl‐ p ‐aminobenzoate moiety (THF tail) is unique. Apart from snapshots of individual reaction steps of MtgA, structure‐based mutagenesis combined with enzymatic activity assays allowed a mechanistic description of the methyl transfer between Cbl‐CH 3 and THF. Altogether, the THF‐tail‐binding motion observed in MtgA is unique compared to other THF methyltransferases and therefore contributes to the general understanding of THF‐mediated methyl transfer.