8SSD

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

8SSD の概要

• エントリーDOI: 10.2210/pdb8ssd/pdb
• 分子名称: Methionine synthase (2 entities in total)
• 機能のキーワード: methyl transferase, cobalamin-dependent, methionine synthase, cobalamin binding, one-carbon metabolism, transferase
• 由来する生物種: Thermus thermophilus HB8
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 175816.32

構造登録者

Yamada, K.,Mendoza, J.,Koutmos, M. (登録日: 2023-05-08, 公開日: 2023-10-11, 最終更新日: 2024-05-01)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.4 Å)