4O1E

Structure of a methyltransferase component in complex with MTHF involved in O-demethylation

Summary for 4O1E

• Entry DOI: 10.2210/pdb4o1e/pdb
• Related: 4O0Q 4O1F
• Descriptor: Dihydropteroate synthase DHPS, 5-METHYL-5,6,7,8-TETRAHYDROFOLIC ACID (3 entities in total)
• Functional Keywords: tim barrel, methyltransferase, thf/mthf, transferase
• Biological source: Desulfitobacterium hafniense
• Total number of polymer chains: 2
• Total formula weight: 64429.88

Authors

Sjuts, H.,Dunstan, M.S.,Fisher, K.,Leys, D. (deposition date: 2013-12-15, release date: 2015-01-21, Last modification date: 2024-03-20)

Primary citation

Sjuts, H.,Dunstan, M.S.,Fisher, K.,Leys, D.
Structures of the methyltransferase component of Desulfitobacterium hafniense DCB-2 O-demethylase shed light on methyltetrahydrofolate formation
Acta Crystallogr.,Sect.D, 71:1900-1908, 2015

PubMed 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.

PubMed: 26327380
DOI: 10.1107/S1399004715013061

Experimental method

X-RAY DIFFRACTION (1.61 Å)