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Structures of the methyltransferase component of Desulfitobacterium hafniense DCB-2 O-demethylase shed light on methyltetrahydro­folate formation

DOI: 10.1107/S1399004715013061 DOI Help
PMID: 26327380 PMID Help

Authors: Hanno Sjuts (University of Manchester) , Mark Dunstan (University of Manchester) , Karl Fisher (Manchester Institute of Biotechnology) , David Leys (School of Chemistry & Manchester Interdisciplinary Biocentre, The University of Manchester)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section D Biological Crystallography , VOL 71 , PAGES 1900 - 1908

State: Published (Approved)
Published: September 2015
Diamond Proposal Number(s): 7146 , 8997

Open Access Open Access

Abstract: O-Demethylation by acetogenic or organohalide-respiring bacteria leads to the formation of methyltetrahydrofolate from aromatic methyl ethers. O-Demethylases, which are cobalamin-dependent, three-component enzyme systems, catalyse methyl-group transfers from aromatic methyl ethers to tetrahydrofolate via methylcobalamin intermediates. In this study, crystal structures of the tetrahydrofolate-binding methyltransferase module from a Desulfitobacterium hafniense DCB-2 O-demethylase were determined both in complex with tetrahydrofolate and the product methyltetrahydrofolate. While these structures are similar to previously determined methyltransferase structures, the position of key active-site residues is subtly altered. A strictly conserved Asn is displaced to establish a putative proton-transfer network between the substrate N5 and solvent. It is proposed that this supports the efficient catalysis of methyltetra­hydrofolate formation, which is necessary for efficient O-demethylation.

Journal Keywords: Methyltransferase; O-Demethylation; Crystal Structure; Methyltetrahydrofolate

Subject Areas: Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography