Methionine synthase
From Proteopedia
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The change from homocysteine to methionine is an SN2 reaction, as seen above, where the methyl group from methyltetrahydrofolate (MTHF), located on N-5, is donated. MTHF is a product of Methylenetetrahydrofolate reductase (MTHFR). | The change from homocysteine to methionine is an SN2 reaction, as seen above, where the methyl group from methyltetrahydrofolate (MTHF), located on N-5, is donated. MTHF is a product of Methylenetetrahydrofolate reductase (MTHFR). | ||
| - | This is a complex reaction as the product, tetrahydrofolate, is a poor leaving group, thus requiring a "super nucleophile"<ref>DOI: 10.1038/nature10916</ref> with a protein-bound vitamin B12 cobalamin as the methyl carrier. | + | This is a complex reaction as the product, tetrahydrofolate, is a poor leaving group, thus requiring a "super nucleophile"<ref name="nature et al">DOI: 10.1038/nature10916</ref> with a protein-bound vitamin B12 cobalamin as the methyl carrier. |
== Relevance == | == Relevance == | ||
| - | Methionine deficiency can result in diseases such as birth abnormalities<ref | + | Methionine deficiency can result in diseases such as birth abnormalities<ref name="nature et al"/>. |
<StructureSection load='1k7y' size='310' side='right' caption='B12 dependent fragment of E. coli methionine synthase with Cobalt (in pink)' scene=''> | <StructureSection load='1k7y' size='310' side='right' caption='B12 dependent fragment of E. coli methionine synthase with Cobalt (in pink)' scene=''> | ||
Revision as of 14:56, 6 April 2022
Methionine synthase
This page is being worked on during the Spring 2022 semester.
Methionine is an essential amino acid required by our bodies for healthy cell and tissue growth. It is essential as it is not naturally derived, and is obtained from our diet first in the form of homocysteine. Methionine synthase (MetH; EC: 2.1.1.13) is a B12-dependent enzyme that methylates homocysteine to regenerate methionine as needed.
The change from homocysteine to methionine is an SN2 reaction, as seen above, where the methyl group from methyltetrahydrofolate (MTHF), located on N-5, is donated. MTHF is a product of Methylenetetrahydrofolate reductase (MTHFR).
This is a complex reaction as the product, tetrahydrofolate, is a poor leaving group, thus requiring a "super nucleophile"[1] with a protein-bound vitamin B12 cobalamin as the methyl carrier.
Relevance
Methionine deficiency can result in diseases such as birth abnormalities[1].
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References
- ↑ 1.0 1.1 Kung Y, Ando N, Doukov TI, Blasiak LC, Bender G, Seravalli J, Ragsdale SW, Drennan CL. Visualizing molecular juggling within a B(12)-dependent methyltransferase complex. Nature. 2012 Mar 14. doi: 10.1038/nature10916. PMID:22419154 doi:10.1038/nature10916
- ↑ Bandarian V, Pattridge KA, Lennon BW, Huddler DP, Matthews RG, Ludwig ML. Domain alternation switches B(12)-dependent methionine synthase to the activation conformation. Nat Struct Biol. 2002 Jan;9(1):53-6. PMID:11731805 doi:10.1038/nsb738
- ↑ Barra L, Fontenelle C, Ermel G, Trautwetter A, Walker GC, Blanco C. Interrelations between glycine betaine catabolism and methionine biosynthesis in Sinorhizobium meliloti strain 102F34. J Bacteriol. 2006 Oct;188(20):7195-204. doi: 10.1128/JB.00208-06. PMID:17015658 doi:http://dx.doi.org/10.1128/JB.00208-06
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