Structure of full-length cobalamin-dependent methionine synthase and cofactor loading captured in crystallo.

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-bindin

SUBMITTER: Mendoza J 

PROVIDER: S-EPMC10567725 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature