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- Title
Domain alternation switches B(12)-dependent methionine synthase to the activation conformation.
- Authors
Bandarian, Vahe; Pattridge, Katherine A; Lennon, Brett W; Huddler, Donald P; Matthews, Rowena G; Ludwig, Martha L
- Abstract
B(12)-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 A 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 A and rotates by 63 degrees, 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.
- Publication
Nature structural biology, 2002, Vol 9, Issue 1, p53
- ISSN
1072-8368
- Publication type
Journal Article
- DOI
10.1038/nsb738