Methionine synthase
From Proteopedia
(Difference between revisions)
| Line 3: | Line 3: | ||
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 | + | 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) is a B12-dependent enzyme that methylates 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), 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 name="Kung et al">DOI: 10.1038/nature10916</ref>, where the vitamin B12 cobalamin, comes in 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="Kung et al">DOI: 10.1038/nature10916</ref> | + | |
== Relevance == | == Relevance == | ||
| Line 18: | Line 16: | ||
== Structural highlights == | == Structural highlights == | ||
| - | The <scene name='90/907471/Superposition_1/2'>full structure of | + | 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 of vitamin B12 cobalamin (in pink), methyltetrahydrofolate (in blue), homocysteine (in yellow), and SAH (in red; as part of the SAM cycle). Each domain with an important function required for both catalytic and reactivation cycles<ref>DOI: 10.1038/nsb738</ref> of MS. |
| Line 24: | Line 22: | ||
== Vitamin B12 == | == Vitamin B12 == | ||
| - | PDB ID: 1K7Y refers to the B12 domain of | + | PDB ID: 1K7Y refers to the B12 domain of MS. |
== Oxidation States of Cobalamin == | == Oxidation States of Cobalamin == | ||
| + | |||
| + | 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. | ||
Co(I) - active, unstable, high energy | Co(I) - active, unstable, high energy | ||
Revision as of 16:18, 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 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) 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], where the vitamin B12 cobalamin, comes in as the methyl carrier.
Relevance
Methionine deficiency can result in diseases such as birth abnormalities[1].
| |||||||||||
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
Proteopedia Page Contributors and Editors (what is this?)
Kia Yang, Karsten Theis, Michal Harel, Anna Postnikova, Michael O'Shaughnessy
