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Instruments / Technical Area	Publication Details	Published	Actions
B21-High Throughput SAXS I04-1-Macromolecular Crystallography (fixed wavelength)	Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition D. Sean Froese , Jolanta Kopec , Elzbieta Rembeza , Gustavo Arruda Bezerra , Anselm Erich Oberholzer , Terttu Suormala , Seraina Lutz , Rod Chalk , Oktawia Borkowska , Matthias R. Baumgartner , Wyatt W. Yue Nature Communications 9 DOI: 10.1038/s41467-018-04735-2 Diamond Proposal Number(s): [10619, 51433] Open Access Show Abstract ▼ Abstract: The folate and methionine cycles are crucial for biosynthesis of lipids, nucleotides and proteins, and production of the methyl donor S-adenosylmethionine (SAM). 5,10-methylenetetrahydrofolate reductase (MTHFR) represents a key regulatory connection between these cycles, generating 5-methyltetrahydrofolate for initiation of the methionine cycle, and undergoing allosteric inhibition by its end product SAM. Our 2.5 Å resolution crystal structure of human MTHFR reveals a unique architecture, appending the well-conserved catalytic TIM-barrel to a eukaryote-only SAM-binding domain. The latter domain of novel fold provides the predominant interface for MTHFR homo-dimerization, positioning the N-terminal serine-rich phosphorylation region near the C-terminal SAM-binding domain. This explains how MTHFR phosphorylation, identified on 11 N-terminal residues (16 in total), increases sensitivity to SAM binding and inhibition. Finally, we demonstrate that the 25-amino-acid inter-domain linker enables conformational plasticity and propose it to be a key mediator of SAM regulation. Together, these results provide insight into the molecular regulation of MTHFR.	Jun 2018

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B21-High Throughput SAXS
I04-1-Macromolecular Crystallography (fixed wavelength)

Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition