Methionine 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 first in the form of homocysteine.

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 highlights

Methionine synthase (MetH) is a B12-dependent enzyme that methylates homocysteine to regenerate methionine. The has yet to be determined but we understand it contains 4 domains of B12 cobalamin (in pink), methyltetrahydrofolate (blue), homocysteine (yellow), and SAH (as part of the SAM cycle; in red). Each domain with an important function required for catalytic and reactivation cycles.

Vitamin B-12

Oxidation States of Cobalamin

Co(I) - active, unstable, high energy

Co(II) - common oxidation state

Relevance

Methionine deficiency can result in diseases such as birth abnormalities.