Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural insights into cobalamin loading and reactivation of human methionine synthase.
Journal, issue, pages	Nat Commun, Year 2026
Publish date	May 11, 2026
Authors	Douglas S M Ferreira / Katie McLennan / Calum Diamond / Melanie Vollmar / Wasim Kiyani / D Sean Froese / Jola Kopec / Henry J Bailey / Rod Chalk / Arnaud Baslé / Jonathan M Elkins / Jesse A Coker / Wyatt W Yue / Thomas J McCorvie /
PubMed Abstract	Human methionine synthase (MTR) is an essential enzyme of one carbon metabolism. Consisting of a catalytic N-half and a cobalamin binding C-half, MTR utilises this intricate organometallic cofactor ...Human methionine synthase (MTR) is an essential enzyme of one carbon metabolism. Consisting of a catalytic N-half and a cobalamin binding C-half, MTR utilises this intricate organometallic cofactor in the methyl transfer from methyltetrahydrofolate to homocysteine producing methionine. Cobalamin loading into MTR, and its subsequent activation, requires methylmalonic aciduria and homocystinuria Type D (MMADHC) protein and methionine synthase reductase (MTRR), respectively. However, the molecular basis of cobalamin binding and activation of human MTR aided by MMADHC and MTRR remains unknown. Here, using cryo-electron microscopy, we determine structures of human MTR in its apo, and cobalamin bound states. Apo MTR adopts a conformation where the two halves of the enzyme act independently with the C-half posed to bind cobalamin. Binding of cobalamin and its activation causes conformational changes in MTR that result in a flexible catalytically active state. AlphaFold predictions, validated by interaction studies, show that MMADHC interacts with the C-half of apo MTR to facilitate cobalamin loading. Unexpectedly we found that MTRR interacts at two distinct sites within the C-half of MTR which may aid in activation. Collectively these findings lay the groundwork to uncover the mechanisms through how MMADHC and MTRR coordinate cobalamin loading and activation of human MTR.
External links	Nat Commun / PubMed:42115646
Methods	EM (single particle)
Resolution	2.63 - 3.1 Å
Structure data	55190 9ssp EMDB-55190, PDB-9ssp: Human Methionine Synthase With Methyltetrahydrofolate, N-Half From Full-Length Method: EM (single particle) / Resolution: 3.1 Å 55191 9ssq EMDB-55191, PDB-9ssq: Human Methionine Synthase With Methyltetrahydrofolate, C-Half From Full-Length Method: EM (single particle) / Resolution: 2.82 Å 55192 9ssr EMDB-55192, PDB-9ssr: Human Methionine Synthase With Methyltetrahydrofolate, Hydroxocobalamin, and SAM, N-Half From Full-Length Method: EM (single particle) / Resolution: 2.84 Å 55193 9sss EMDB-55193, PDB-9sss: Human Methionine Synthase With Methyltetrahydrofolate, Hydroxocobalamin, and SAM, C-Half His-ON From Full-Length Method: EM (single particle) / Resolution: 3.01 Å 55194 9sst EMDB-55194, PDB-9sst: Human Methionine Synthase With Methyltetrahydrofolate, Hydroxocobalamin, and SAM, C-Half His-OFF From Full-Length Method: EM (single particle) / Resolution: 2.82 Å 55195 9ssu EMDB-55195, PDB-9ssu: Human Methionine Synthase With Methylcobalamin, N-Half From Full-Length Method: EM (single particle) / Resolution: 2.63 Å 55196 9ssv EMDB-55196, PDB-9ssv: Human Methionine Synthase With Methylcobalamin, Activation Domain From Full-Length Method: EM (single particle) / Resolution: 3.09 Å
Chemicals	ChemComp-THH: N-[4-({[(6S)-2-AMINO-4-HYDROXY-5-METHYL-5,6,7,8-TETRAHYDROPTERIDIN-6-YL]METHYL}AMINO)BENZOYL]-L-GLUTAMIC ACID ChemComp-B12: COBALAMIN
Source	homo sapiens (human)
Keywords	TRANSFERASE / Methionine / Folate / Cobalamin