8SSE

Methionine synthase, C-terminal fragment, Cobalamin and Reactivation Domains from Thermus thermophilus HB8

Summary for 8SSE

• Entry DOI: 10.2210/pdb8sse/pdb
• Descriptor: Methionine synthase, COBALAMIN (3 entities in total)
• Functional Keywords: methyl transferase, cobalamin-dependent, methionine synthase, cobalamin binding, one-carbon metabolism, transferase
• Biological source: Thermus thermophilus HB8
• Total number of polymer chains: 6
• Total formula weight: 359614.78

Authors

Yamada, K.,Mendoza, J.,Koutmos, M. (deposition date: 2023-05-08, release date: 2023-10-11, Last modification date: 2024-05-01)

Primary citation

Mendoza, J.,Purchal, M.,Yamada, K.,Koutmos, M.
Structure of full-length cobalamin-dependent methionine synthase and cofactor loading captured in crystallo.
Nat Commun, 14:6365-6365, 2023

PubMed Abstract: Cobalamin-dependent methionine synthase (MS) is a key enzyme in methionine and folate one-carbon metabolism. MS is a large multi-domain protein capable of binding and activating three substrates: homocysteine, folate, and S-adenosylmethionine for methylation. Achieving three chemically distinct methylations necessitates significant domain rearrangements to facilitate substrate access to the cobalamin cofactor at the right time. The distinct conformations required for each reaction have eluded structural characterization as its inherently dynamic nature renders structural studies difficult. Here, we use a thermophilic MS homolog (tMS) as a functional MS model. Its exceptional stability enabled characterization of MS in the absence of cobalamin, marking the only studies of a cobalamin-binding protein in its apoenzyme state. More importantly, we report the high-resolution full-length MS structure, ending a multi-decade quest. We also capture cobalamin loading in crystallo, providing structural insights into holoenzyme formation. Our work paves the way for unraveling how MS orchestrates large-scale domain rearrangements crucial for achieving challenging chemistries.

PubMed: 37821448
DOI: 10.1038/s41467-023-42037-4

Experimental method

X-RAY DIFFRACTION (3.15 Å)