Domain alternation switches B12-dependent methionine synthase to the activation conformation
| Autor: | Katherine A. Pattridge, Vahe Bandarian, Brett W. Lennon, Rowena G. Matthews, Donald P. Huddler, Martha L. Ludwig |
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| Rok vydání: | 2001 |
| Předmět: |
Models
Molecular S-Adenosylmethionine Homocysteine Stereochemistry Movement Crystallography X-Ray 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase Biochemistry Cobalamin Protein Structure Secondary Cofactor chemistry.chemical_compound Structural Biology Escherichia coli polycyclic compounds Genetics Transferase Methionine synthase chemistry.chemical_classification Binding Sites biology nutritional and metabolic diseases Meth Peptide Fragments Protein Structure Tertiary Enzyme Activation Vitamin B 12 Enzyme chemistry biology.protein Binding domain |
| Zdroj: | Nature Structural Biology. 9:53-56 |
| ISSN: | 1072-8368 |
| DOI: | 10.1038/nsb738 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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