Methionine synthase
From Proteopedia
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This page is being worked on during the Spring 2022 semester. | 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 because is not naturally derived, and must be obtained from our diet first in the form of homocysteine. Methionine synthase (abbrev. MS; EC: 2.1.1.13) | + | Methionine is an essential amino acid required by our bodies for healthy cell and tissue growth. It is essential because is not naturally derived, and must be obtained from our diet first in the form of homocysteine. Methionine synthase (abbrev. MS; EC: 2.1.1.13), a B12-dependent enzyme, catalyzes the methylation of homocysteine to regenerate methionine as needed. |
[[Image:Overall.jpeg]] | [[Image:Overall.jpeg]] | ||
| - | The change from homocysteine to methionine is an SN2 reaction, as seen above, where the methyl group from methyltetrahydrofolate (MTHF) | + | The change from homocysteine to methionine is an SN2 reaction, as seen above, where the methyl group on N-5 from methyltetrahydrofolate (MTHF), is donated. MTHF is a product of Methylenetetrahydrofolate reductase (MTHFR) from the folate cycle [link Shaylie's page here]. This is a complex reaction as tetrahydrofolate, the product, is a poor leaving group and thus requiring a "super nucleophile", vitamin B12 cob(I)alamin, to carry out the reaction<ref name="Kung et al">DOI: 10.1038/nature10916</ref>, and becoming the intermediate methyl carrier. |
== Relevance == | == Relevance == | ||
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== Structural highlights == | == Structural highlights == | ||
| - | The <scene name='90/907471/Superposition_1/2'>full structure of MS</scene> has yet to be determined but we understand it contains 4 domains | + | The <scene name='90/907471/Superposition_1/2'>full structure of MS</scene> has yet to be determined but we understand it contains 4 domains, each with an important function required for both catalytic and reduction reactivation cycles <ref>DOI: 10.1038/nsb738</ref>. The domains: vitamin B12 cobalamin as the methyl carrier (in pink), methyltetrahydrofolate as a methyl donor (in blue), homocysteine as another (in yellow), and SAM (in red). of MS. |
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PDB ID: 1K7Y refers to the B12 domain of MS. | PDB ID: 1K7Y refers to the B12 domain of MS. | ||
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| + | In aerobic conditions, vitamin B12 Cobalamin(I) occasionally undergoes oxidation and this leads to an inactive Cob(II)alamin enzyme. A buildup of Cob(II)alamin is This is reactivated to Cob(I)alamin via reductive reactivation cycle with S-adenosylmethionine (SAM) as the methyl donor and Flavodoxin as an electron donor. B12 is unique. Conformations of MS allow substrates to be presented to vitamin B12 Cobalamin. A buildup | ||
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== Oxidation States of Cobalamin == | == Oxidation States of Cobalamin == | ||
Catalytic Cycle: | Catalytic Cycle: | ||
| - | The super nucleophile is with Cobalt in the +1 oxidation state in order to carry through with the SN2 reaction of breaking the bond between THF and the methyl group. | + | The super nucleophile is with Cobalt in the +1 oxidation state in order to carry through with the SN2 reaction of breaking the bond between THF and the methyl group. |
Co(I) - active, unstable, high energy | Co(I) - active, unstable, high energy | ||
| - | Co(II) - common oxidation state | + | Co(II) - common oxidation state, inactive form |
</StructureSection> | </StructureSection> | ||
Revision as of 18:34, 11 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 because is not naturally derived, and must be obtained from our diet first in the form of homocysteine. Methionine synthase (abbrev. MS; EC: 2.1.1.13), a B12-dependent enzyme, catalyzes the methylation of homocysteine to regenerate methionine as needed.
The change from homocysteine to methionine is an SN2 reaction, as seen above, where the methyl group on N-5 from methyltetrahydrofolate (MTHF), is donated. MTHF is a product of Methylenetetrahydrofolate reductase (MTHFR) from the folate cycle [link Shaylie's page here]. This is a complex reaction as tetrahydrofolate, the product, is a poor leaving group and thus requiring a "super nucleophile", vitamin B12 cob(I)alamin, to carry out the reaction[1], and becoming the intermediate 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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