Methionine synthase

Methionine synthaseMethionine synthase

This page is being worked on during the Spring 2022 semester. EC: 2.1.1.13 PDB ID: 1K7Y - cobalamin, 1K98 - AdoMet complex 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 we get it from our diet in the form of homocysteine. Methionine synthase (MetH) is a B12-dependent enzyme that methylates homocysteine to regenerate methionine. The change from homocysteine to methionine is a methyl group. This reaction is regulated by methyltetrahydrofolate (a product from MTFHR) as a methyl donor and B12 as the methyl carrier. The has yet to be determined but we understand it contains 4 domains for its catalytic and its reactivation cycles requiring B12 cobalamin (in pink), methyltetrahydrofolate (blue), homocysteine (yellow), and SAH (as part of the SAM cycle; in red). With activation of methionine synthase, the first domain of B12 is initially in a “capped” position preventing unwanted chemistry from occurring. To uncap the B12 domain, methyltransferase comes in to also assist with the methyl transfer from methyltetrahydrofolate allowing B12 to accept and carry the methyl.

spinqualitylabelsall models B-12 dependent fragment of E. coli methionine synthase with Cobalt (in pink) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

The change from homocysteine to methionine is an SN2 reaction where the methyl group from methyltetrahydrofolate (MTHF), located on N-5, is donated. MTHF is a product of MTHFR.

This is a complex reaction as the product, tetrahydrofolate, is a poor leaving group, thus requiring a "supernucleophile" with a protein-bound B-12 vitamin Cobalamin as the methyl carrier.

Structural highlightsStructural highlights

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.