5-Formyltetrahydrofolate promotes conformational remodeling in a methylenetetrahydrofolate reductase active site and inhibits its activity.

ABSTRACT: The flavoprotein methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of N5, N10-methylenetetrahydrofolate (CH₂-H₄folate) to N5-methyltetrahydrofolate (CH₃-H₄folate), committing a methyl group from the folate cycle to the methionine one. This committed step is the sum of multiple ping-pong electron transfers involving multiple substrates, intermediates, and products all sharing the same active site. Insight into folate substrate binding is needed to better understand this multifunctional active site. Here, we performed activity assays with Thermus thermophilus MTHFR (tMTHFR), which showed pH-dependent inhibition by the substrate analog, N5-formyltetrahydrofolate (CHO-H₄folate). Our crystal structure of a tMTHFR•CHO-H

SUBMITTER: Yamada K 

PROVIDER: S-EPMC9900621 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature