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

@article{Bandarian2002DomainAS,
  title={Domain alternation switches B12-dependent methionine synthase to the activation conformation},
  author={Vahe Bandarian and Katherine A. Pattridge and Brett W. Lennon and Donald P. Huddler and Rowena G. Matthews and Martha Ludwig},
  journal={Nature Structural Biology},
  year={2002},
  volume={9},
  pages={53-56}
}
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… 
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An x-ray structure of the mutant fragment in the reactivation conformation is described; this conformation enables the transfer of a methyl group from AdoMet to the cobalamin cofactor.
Factors modulating conformational equilibria in large modular proteins: A case study with cobalamin-dependent methionine synthase
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Probing the role of the histidine 759 ligand in cobalamin-dependent methionine synthase.
TLDR
The formation of this four-coordinate cob(II)alamin "dead-end" species in the His759Gly variant illustrates the importance of the His758 residue in governing the equilibria between the different conformations of MetH.
Structures of the N-terminal modules imply large domain motions during catalysis by methionine synthase.
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TLDR
The authors' studies on cob(III)alamins bound to MetH, specifically aqua-, methyl-, and n-propylcobalamin, show a correlation between the accessibility of the reactivation conformation and the order of the established ligand trans influence, which controls the affinity of MetH in the cob( III)alamin form for flavodoxin.
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The structure of s-sMetHCT with cob(II)alamin and S-adenosyl-L-homocysteine represents the enzyme in the reactivation step preceding electron transfer from flavodoxin, and supports earlier suggestions that the enzyme acts to lower the reduction potential of the Co(II)/Co(I) couple by elongating the bond between the cobalt and its upper axial water ligand.
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Visualising molecular juggling within a B12-dependent methyltransferase complex
TLDR
These structures provide the first three-dimensional depiction of all protein modules required for the activation, protection and catalytic steps of B12-dependent methyl transfer, and are presented alongside in crystallo spectroscopic data, which confirm enzymatic activity within crystals and demonstrate the largest known conformational movements of proteins in a crystalline state.
Visualizing molecular juggling within a B[subscript 12]-dependent methyltransferase complex
Derivatives of vitamin B12 are used in methyl group transfer in biological processes as diverse as methionine synthesis in humans and CO2 fixation in acetogenic bacteria1–3. This seemingly
Conformational dynamics in the Acyl-CoA synthetases, adenylation domains of non-ribosomal peptide synthetases, and firefly luciferase.
  • A. Gulick
  • Chemistry, Biology
    ACS chemical biology
  • 2009
TLDR
Support for this domain alternation strategy is presented along with an explanation of the advantage of this catalytic strategy for the reaction catalyzed by the ANL enzymes and the ramifications of this domain rotation in the catalytic cycle of the modular NRPS enzymes are discussed.
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TLDR
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TLDR
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TLDR
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