metH (PP_2375) encodes a large cobalamin-dependent methionine synthase that catalyzes the terminal methylation of L-homocysteine to L-methionine using 5-methyltetrahydrofolate and a methylcobalamin cofactor. It provides the vitamin B12-dependent terminal route for de novo L-methionine biosynthesis in KT2440; the apparent MetE-like proteins in this proteome are partial-domain candidates rather than confirmed cobalamin-independent alternatives.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005829 cytosol | IEA GO_REF:0000118 | ACCEPT | Summary: Cytosol is appropriate for the soluble MetH methionine synthase. Reason: MetH is a soluble cytosolic enzyme catalyzing homocysteine methylation in amino-acid biosynthesis. Supporting Evidence: file:PSEPK/metH/metH-uniprot.txt Methionine synthase |
| GO:0008168 methyltransferase activity | IEA GO_REF:0000104 | MODIFY | Summary: Generic methyltransferase activity should be replaced by the specific methionine synthase activity. Reason: MetH catalyzes the cobalamin-dependent methyl transfer from 5-methyltetrahydrofolate to homocysteine; GO:0008705 is already present and is the specific activity. Proposed replacements: methionine synthase activity Supporting Evidence: file:PSEPK/metH/metH-uniprot.txt Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + L-homocysteine = |
| GO:0008270 zinc ion binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Zinc ion binding is a catalytic metal feature of MetH. Reason: The zinc-binding homocysteine domain supports the methionine synthase mechanism, but the core function is the methyltransferase reaction. Supporting Evidence: file:PSEPK/metH/metH-uniprot.txt Name=Zn(2+) |
| GO:0008705 methionine synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Methionine synthase activity is the core MetH molecular function. Reason: UniProt describes the cobalamin-dependent reaction converting 5-methyltetrahydrofolate and homocysteine to tetrahydrofolate and methionine, matching EC 2.1.1.13/Rhea:11172 and GO:0008705. Supporting Evidence: file:PSEPK/metH/metH-uniprot.txt EC=2.1.1.13 file:PSEPK/metH/metH-uniprot.txt PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo file:PSEPK/metH/metH-deep-research-openscientist.md Q88KB5 carries the complete four-module domain architecture diagnostic of the MetH family |
| GO:0016740 transferase activity | IEA GO_REF:0000104 | MODIFY | Summary: Generic transferase activity should be replaced by methionine synthase activity. Reason: GO:0008705 is the specific transferase activity for this enzyme and is already present in the GOA table; the curated reaction is methionine synthase. Proposed replacements: methionine synthase activity Supporting Evidence: file:PSEPK/metH/metH-uniprot.txt Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + L-homocysteine = |
| GO:0031419 cobalamin binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Cobalamin binding is a key MetH cofactor-binding activity. Reason: The methylcobalamin cofactor is required for MetH catalysis, but the core molecular function remains methionine synthase activity. Supporting Evidence: file:PSEPK/metH/metH-uniprot.txt Name=methylcob(III)alamin |
| GO:0042558 pteridine-containing compound metabolic process | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Pteridine-containing compound metabolism is a cofactor-side annotation rather than the core MetH process. Reason: MetH uses 5-methyltetrahydrofolate, but the biologically specific process for this enzyme is L-methionine biosynthesis, not a broad pteridine-metabolism process. Supporting Evidence: file:PSEPK/metH/metH-uniprot.txt L-methionine from L-homocysteine (MetH route): step 1/1 |
| GO:0046653 tetrahydrofolate metabolic process | IEA GO_REF:0000118 | KEEP AS NON CORE | Summary: Tetrahydrofolate metabolism is relevant to MetH cofactor cycling but non-core. Reason: MetH remethylates its cobalamin cofactor using methyltetrahydrofolate, so tetrahydrofolate metabolism is related but secondary to methionine biosynthesis. Supporting Evidence: file:PSEPK/metH/metH-uniprot.txt remethylates the cofactor using methyltetrahydrofolate |
| GO:0046872 metal ion binding | IEA GO_REF:0000002 | MODIFY | Summary: Metal ion binding is correct but less specific than the zinc-binding annotation already present. Reason: UniProt and GOA specify zinc ion binding for MetH, so the generic metal-ion binding term should be replaced by GO:0008270. Proposed replacements: zinc ion binding Supporting Evidence: file:PSEPK/metH/metH-uniprot.txt Name=Zn(2+) |
| GO:0050667 homocysteine metabolic process | IEA GO_REF:0000118 | MODIFY | Summary: Homocysteine metabolic process is correct but too broad for the terminal methionine-biosynthesis reaction. Reason: MetH consumes homocysteine to make methionine in the de novo methionine biosynthesis pathway; L-methionine biosynthetic process is the better process term. Proposed replacements: L-methionine biosynthetic process Supporting Evidence: file:PSEPK/metH/metH-uniprot.txt L-methionine from L-homocysteine (MetH route): step 1/1 |
| GO:0071267 L-methionine salvage | IEA GO_REF:0000108 | MODIFY | Summary: L-methionine salvage is not the right process for canonical MetH. Reason: The GOA rule inferred this term from methionine synthase activity, but UniProt places MetH in de novo L-methionine biosynthesis from homocysteine, not in methionine salvage. Proposed replacements: L-methionine biosynthetic process Supporting Evidence: file:PSEPK/metH/metH-uniprot.txt PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo |
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Download this section (compressed HTML)Q: Under which KT2440 growth conditions is the MetH route limited by cobalamin biosynthesis, salvage, or uptake rather than by the methionine-pathway enzymes themselves?
Experiment: Compare metH mutant growth in defined media with controlled vitamin B12, cobalt, methionine, and homocysteine supplementation, and test whether partial MetE-like proteins can rescue the terminal methylation step in trans.
Type: targeted genetics and nutrient rescue
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