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'

Journal Article · Mon Jan 01 00:00:00 EST 2018 · Acta Crystallographica. Section D. Structural Biology

DOI:https://doi.org/10.1107/S2059798317018290· OSTI ID:1502231

Yamada, Kazuhiro ; Koutmos, Markos

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 S_N2-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 fromThermus thermophilusis 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 β₈α₈fold found in all other folate-binding domains, MS Fol domains exhibit a unique β₈α₇fold. It is posited that these structural differences are important for MS function.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: AHA
• OSTI ID: 1502231
• Journal Information: Acta Crystallographica. Section D. Structural Biology, Vol. 74, Issue 1; ISSN 2059-7983
• Publisher: IUCr
• Country of Publication: United States
• Language: ENGLISH