Methionine synthase: Difference between revisions

MS is a B12-dependent enzyme responsible for regenerating methionine from homocysteine and uses vitamin B12 Cobalamin as a cofactor. The change from homocysteine to methionine is an SN2 reaction, as seen above, where the methyl group on N-5 from 5-me THF, is donated. 5-me THF is a product of methylenetetrahydrofolate reductase [[MTHFR]] from the folate cycle. This is a complex reaction as tetrahydrofolate (THF), the product, is a poor leaving group and requires a "super nucleophile", Cob(I)alamin, to carry out the reaction<ref>DOI:10.1146/annurev.biochem.72.121801.161828</ref><ref name="Kung et al">DOI: 10.1038/nature10916</ref> as a methyl carrier.

== Oxidation States of Cobalamin ==  

=== Cobalamin activation ===

<scene name='90/907471/B12_activation_w_sah/1'>B12 activation</scene>. This structure uses the mutant H759G to maximise the fraction of enzyme with the B12 domain in the cap-off conformation bound to the activation domain. The approach of the B12 domain and the activation domain has to be carefully regulated because methylating homocysteine with methyl groups from S-adenosyl methionine results in a futile cycle. Thus, this step should be reserved to rescue B12 out of the +2 cobalt oxidation state, and then methylation of homocysteine using a methyl group from 5-me THF resumes.