Domain alternation switches B12-dependent methionine synthase to the activation conformation

Vahe Bandarian, K. A. Pattridge, B. W. Lennon, D. P. Huddler, R. G. Matthews, M. L. Ludwig

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

B12-dependent methionine synthase (MetH) from Escherichia coli is a large modular protein that uses bound cobalamin as an intermediate methyl carrier. Major domain rearrangements have been postulated to explain how cobalamin reacts with three different substrates: homocysteine, methyltetrahydrofolate and S-adenosylmethionine (AdoMet). Here we describe the 3.0 Å structure of a 65 kDa C-terminal fragment of MetH that spans the cobalamin- and AdoMet-binding domains, arranged in a conformation suitable for the methyl transfer from AdoMet to cobalamin that occurs during activation. In the conversion to the activation conformation, a helical domain that capped the cofactor moves 26 Å and rotates by 63°, allowing formation of a new interface between cobalamin and the AdoMet-binding (activation) domain. Interactions with the MetH activation domain drive the cobalamin away from its binding domain in a way that requires dissociation of the axial cobalt ligand and, thereby, provide a mechanism for control of the distribution of enzyme conformations.

Original languageEnglish (US)
Pages (from-to)53-56
Number of pages4
JournalNature Structural Biology
Volume9
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

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5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
Vitamin B 12
Conformations
Chemical activation
Switches
S-Adenosylmethionine
Homocysteine
Cobalt
Escherichia coli
Ligands
Substrates
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Genetics

Cite this

Bandarian, V., Pattridge, K. A., Lennon, B. W., Huddler, D. P., Matthews, R. G., & Ludwig, M. L. (2002). Domain alternation switches B12-dependent methionine synthase to the activation conformation. Nature Structural Biology, 9(1), 53-56. https://doi.org/10.1038/nsb738

Domain alternation switches B12-dependent methionine synthase to the activation conformation. / Bandarian, Vahe; Pattridge, K. A.; Lennon, B. W.; Huddler, D. P.; Matthews, R. G.; Ludwig, M. L.

In: Nature Structural Biology, Vol. 9, No. 1, 2002, p. 53-56.

Research output: Contribution to journalArticle

Bandarian, V, Pattridge, KA, Lennon, BW, Huddler, DP, Matthews, RG & Ludwig, ML 2002, 'Domain alternation switches B12-dependent methionine synthase to the activation conformation', Nature Structural Biology, vol. 9, no. 1, pp. 53-56. https://doi.org/10.1038/nsb738
Bandarian, Vahe ; Pattridge, K. A. ; Lennon, B. W. ; Huddler, D. P. ; Matthews, R. G. ; Ludwig, M. L. / Domain alternation switches B12-dependent methionine synthase to the activation conformation. In: Nature Structural Biology. 2002 ; Vol. 9, No. 1. pp. 53-56.
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