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Publication Abstract from PubMed

Methyl transfer between methyltetrahydrofolate and corrinoid molecules is a key reaction in biology that is catalyzed by a number of enzymes in many prokaryotic and eukaryotic organisms. One classic example of such an enzyme is cobalamin-dependent methionine synthase (MS). MS is a large modular protein that utilizes an SN2-type mechanism to catalyze the chemically challenging methyl transfer from the tertiary amine (N5) of methyltetrahydrofolate to homocysteine in order to form methionine. Despite over half a century of study, many questions remain about how folate-dependent methyltransferases, and MS in particular, function. Here, the structure of the folate-binding (Fol) domain of MS from Thermus thermophilus is reported in the presence and absence of methyltetrahydrofolate. It is found that the methyltetrahydrofolate-binding environment is similar to those of previously described methyltransferases, highlighting the conserved role of this domain in binding, and perhaps activating, the methyltetrahydrofolate substrate. These structural studies further reveal a new distinct and uncharacterized topology in the C-terminal region of MS Fol domains. Furthermore, it is found that in contrast to the canonical TIM-barrel beta8alpha8 fold found in all other folate-binding domains, MS Fol domains exhibit a unique beta8alpha7 fold. It is posited that these structural differences are important for MS function.

The folate-binding module of Thermus thermophilus cobalamin-dependent methionine synthase displays a distinct variation of the classical TIM barrel: a TIM barrel with a `twist'.,Yamada K, Koutmos M Acta Crystallogr D Struct Biol. 2018 Jan 1;74(Pt 1):41-51. doi:, 10.1107/S2059798317018290. Epub 2018 Jan 1. PMID:29372898^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.