6SJS

Methyltransferase of the MtgA N227A mutant from Desulfitobacterium hafniense in complex with methyl-tetrahydrofolate

Summary for 6SJS

• Entry DOI: 10.2210/pdb6sjs/pdb
• Descriptor: Tetrahydromethanopterin S-methyltransferase, N-[4-({[(6S)-2-AMINO-4-HYDROXY-5-METHYL-5,6,7,8-TETRAHYDROPTERIDIN-6-YL]METHYL}AMINO)BENZOYL]-L-GLUTAMIC ACID, SODIUM ION, ... (5 entities in total)
• Functional Keywords: anaerobic bacteria, glycine betaine metabolism, methyl transfer, cobalamin, tetrahydrofolate, transferase
• Biological source: Desulfitobacterium hafniense DCB-2
• Total number of polymer chains: 2
• Total formula weight: 68355.85

Authors

Badmann, T.,Groll, M. (deposition date: 2019-08-13, release date: 2019-09-25, Last modification date: 2024-01-24)

Primary citation

Badmann, T.,Groll, M.
Structures in Tetrahydrofolate Methylation in Desulfitobacterial Glycine Betaine Metabolism at Atomic Resolution.
Chembiochem, 21:776-779, 2020

PubMed Abstract: 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 ) 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 ) 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 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.

PubMed: 31518049
DOI: 10.1002/cbic.201900515

Experimental method

X-RAY DIFFRACTION (1.8 Å)