Query: 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity (GO:0003871)/Methionine synthase ?

[ValWood]

• Term to be merged: Provide GO ID and term label

GO:0008705 Methionine synthase methionine synthase activity Catalysis of the reaction: (6S)-5-methyl-5,6,7,8-tetrahydrofolate + L-homocysteine = (6S)-5,6,7,8-tetrahydrofolate + L-methionine.

appears to be the same as GO:0003871 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity (GO:0003871) Catalysis of the reaction: 5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = L-methionine + tetrahydropteroyltri-L-glutamate.

BOth terms are used to annotate "methionine synthase"

- CHAT -GPT Yes, the reaction you described:

5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine → L-methionine

• tetrahydropteroyltri-L-glutamate 5-methyltetrahydropteroyltri-L-glutamate+L-homocysteine→L-methionine+tetrahydropteroyltri-L-glutamate

is catalyzed by the enzyme methionine synthase.

Methionine synthase is responsible for the transfer of a methyl group from 5-methyltetrahydrofolate (a form of folate, also referred to as 5-methyltetrahydropteroyltri-L-glutamate) to L-homocysteine, resulting in the formation of L-methionine and tetrahydrofolate (tetrahydropteroyltri-L-glutamate).

( I need to look further into this but I don't want to lose my place!)

• Which term do you propose this term merge into? Provide GO ID and term label

• Reason for merge

• Reference(s) PMID:nnnnnn

• Any other information

[ValWood]

GO:0003871 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity Catalysis of the reaction: 5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = L-methionine + tetrahydropteroyltri-L-glutamate.

GO:0008705 methionine synthase activity Catalysis of the reaction: (6S)-5-methyl-5,6,7,8-tetrahydrofolate + L-homocysteine = (6S)-5,6,7,8-tetrahydrofolate + L-methionine.

[ValWood]

Actually they both have Rhea,

RHEA | 11172 GO:0008705 methionine synthase activity

need to figure out if methionine synthase (yeast) performs both reactions

[ValWood]

CHATGPT The term "methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase" is more specific about the substrate involved (polyglutamated form), while "methionine synthase" is a broader term encompassing all enzymes that catalyze the conversion of homocysteine to methionine using any form of 5-methyltetrahydrofolate

So I am still not sure how to resolve this. It seems that

GO:0003871 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity is a type of GO:0008705 methionine synthase activity?

I don't feel confident to resolve this correctly so I'm going to unassign myself.

[raymond91125]

GO:0003871 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity XREF EC:2.1.1.14, RHEA:21196 GO:0008705 methionine synthase activity XREF EC:2.1.1.13, RHEA:11172 The source of CH3 appears different. Need sources to backup ChatGPT, I think.

[ValWood]

More background:

Background: At PomBAse, historically we annotated methionine synthase/homocysteine methyltransferase https://www.pombase.org/gene/SPAC9.09 Met26 using

GO:0003871 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity  Definition Catalysis of the reaction: 5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = L-methionine +5-methyltetrahydropteroyltri-L-glutamate.

and GO:0003871 is used in my model: http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?barista_token=sasgrjd2nx44ugmbfn3w&model_id=gomodel:66a3e0bb00001342

Then I came across https://www.ebi.ac.uk/QuickGO/term/GO:0008705 methionine synthase Catalysis of the reaction: (6S)-5-methyl-5,6,7,8-tetrahydrofolate + L-homocysteine = (6S)-5,6,7,8-tetrahydrofolate + L-methionine.

so I wondered why this was not used instead? It seems that I could use either, I was not sure if I should annotate to both reactions?

apparently the difference is

(6S)-5-methyl-5,6,7,8-tetrahydrofolate (5-MTHF/L-methylfolate.): This is the simplest form of the reduced, methylated folate molecule with a single glutamate residue attached.

5-methyltetrahydropteroyltri-L-glutamate: This is a polyglutamated form of 5-MTHF with three glutamate residues attached. The additional glutamate residues are added by the enzyme folylpolyglutamate synthetase, increasing the molecule's retention and functionality within cells.

The other difference I have found is that https://enzyme.expasy.org/EC/2.1.1.13 (methionine synthase) is cobalamin-dependent

but https://enzyme.expasy.org/EC/2.1.1.14 5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase (Alternative name cobalamin-independent methionine synthase) is cobalamin independent.

Yeast cobalamin synthase is not cobalamin-dependent https://www.yeastgenome.org/reference/S000086090 so I think the original term I am using is the correct one.

However, these EC/2.1.1.13 / EC/2.1.1.14 are both "methionine synthase" and should have a grouping term in GO. (It might even be clearer to call GO:0003871 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity  "cobalamin-dependent methionine synthase" as a primary term label)

The current arrangements is difficult to figure out from a curation perspective:

[ValWood]

Another problem is excessive grouping terms, both parents of these 2 terms are single inheritance, even though the biologically relevent grouping term is missing.