Domain alternation switches B12-dependent methionine synthase to the activation conformation
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, methyltetrahydrofol...
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Veröffentlicht in: | Nature Structural Biology 2002-01, Vol.9 (1), p.53-56 |
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Sprache: | eng |
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Zusammenfassung: | 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 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. |
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ISSN: | 1072-8368 1545-9993 1545-9985 |
DOI: | 10.1038/nsb738 |