Q49775 · METH_MYCLE
- ProteinMethionine synthase
- GenemetH
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1206 (go to sequence)
- Protein existenceInferred from homology
- Annotation score3/5
Function
function
Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate (By similarity).
Miscellaneous
L-homocysteine is bound via the zinc atom.
Catalytic activity
- (6S)-5-methyl-5,6,7,8-tetrahydrofolate + L-homocysteine = (6S)-5,6,7,8-tetrahydrofolate + L-methionine
Cofactor
Protein has several cofactor binding sites:
Note: Binds 1 zinc ion per subunit.
Pathway
Amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-methionine from L-homocysteine (MetH route): step 1/1.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 233 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 299 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 300 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 750-754 | methylcob(III)alamin (UniProtKB | ChEBI) | ||||
Sequence: GDVHD | ||||||
Binding site | 753 | Co (UniProtKB | ChEBI) of methylcob(III)alamin (UniProtKB | ChEBI); axial binding residue | ||||
Sequence: H | ||||||
Binding site | 798 | methylcob(III)alamin (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 856 | methylcob(III)alamin (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 954 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 1149 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 1203-1204 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: YF |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | cobalamin binding | |
Molecular Function | methionine synthase activity | |
Molecular Function | zinc ion binding | |
Biological Process | methylation | |
Biological Process | pteridine-containing compound metabolic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMethionine synthase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageBacteria > Actinomycetota > Actinomycetes > Mycobacteriales > Mycobacteriaceae > Mycobacterium
Accessions
- Primary accessionQ49775
- Secondary accessions
Proteomes
Organism-specific databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000204533 | 1-1206 | Methionine synthase | |||
Sequence: MRVTAANQHQYDTDLLETLAQRVMVGDGAMGTQLQDAELTLDDFRGLEGCNEILNETRPDVLETIHRRYFEAGADLVETNTFGCNLSNLGDYDIADKIRDLSQRGTVIARRVADELTTPDHKRYVLGSMGPGTKLPTLGHTEYRVVRDAYTESALGMLDGGADAVLVETCQDLLQLKAAVLGSRRAMTQAGRHIPVFVHVTVETTGTMLLGSEIGAALAAVEPLGVDMIGLNCATGPAEMSEHLRHLSKHARIPVSVMPNAGLPVLGAKGAEYPLQPDELAEALAGFIAEFGLSLVGGCCGTTPDHIREVAAAVARCNDGTVPRGERHVTYEPSVSSLYTAIPFAQKPSVLMIGERTNANGSKVFREAMIAEDYQKCLDIAKDQTRGGAHLLDLCVDYVGRNGVADMKALAGRLATVSTLPIMLDSTEIPVLQAGLEHLGGRCVINSVNYEDGDGPESRFVKTMELVAEHGAAVVALTIDEQGQARTVEKKVEVAERLINDITSNWGVDKSAILIDCLTFTIATGQEESRKDGIETIDAIRELKKRHPAVQTTLGLSNISFGLNPSARQVLNSVFLHECQEAGLDSAIVHASKILPINRIPEEQRQAALDLVYDRRREGYDPLQKLMWLFKGVSSPSSKETREAELAKLPLFDRLAQRIVDGERNGLDVDLDEAMTQKPPLAIINENLLDGMKTVGELFGSGQMQLPFVLQSAEVMKAAVAYLEPHMEKSDCDFGKGLAKGRIVLATVKGDVHDIGKNLVDIILSNNGYEVVNLGIKQPITNILEVAEDKSADVVGMSGLLVKSTVIMKENLEEMNTRGVAEKFPVLLGGAALTRSYVENDLAEVYEGEVHYARDAFEGLKLMDTIMSAKRGEALAPGSPESLAAEADRNKETERKARHERSKRIAVQRKAAEEPVEVPERSDVPSDVEVPAPPFWGSRIIKGLAVADYTGFLDERALFLGQWGLRGVRGGAGPSYEDLVQTEGRPRLRYWLDRLSTYGVLAYAAVVYGYFPAVSEDNDIVVLAEPRPDAEQRYRFTFPRQQRGRFLCIADFIRSRDLATERSEVDVLPFQLVTMGQPIADFVGELFVSNSYRDYLEVHGIGVQLTEALAEYWHRRIREELKFSGNRTMSADDPEAVEDYFKLGYRGARFAFGYGACPDLEDRIKMMELLQPERIGVTISEELQLHPEQSTDAFVLHHPAAKYFNV |
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1-314 | Hcy-binding | ||||
Sequence: MRVTAANQHQYDTDLLETLAQRVMVGDGAMGTQLQDAELTLDDFRGLEGCNEILNETRPDVLETIHRRYFEAGADLVETNTFGCNLSNLGDYDIADKIRDLSQRGTVIARRVADELTTPDHKRYVLGSMGPGTKLPTLGHTEYRVVRDAYTESALGMLDGGADAVLVETCQDLLQLKAAVLGSRRAMTQAGRHIPVFVHVTVETTGTMLLGSEIGAALAAVEPLGVDMIGLNCATGPAEMSEHLRHLSKHARIPVSVMPNAGLPVLGAKGAEYPLQPDELAEALAGFIAEFGLSLVGGCCGTTPDHIREVAAAV | ||||||
Domain | 350-609 | Pterin-binding | ||||
Sequence: VLMIGERTNANGSKVFREAMIAEDYQKCLDIAKDQTRGGAHLLDLCVDYVGRNGVADMKALAGRLATVSTLPIMLDSTEIPVLQAGLEHLGGRCVINSVNYEDGDGPESRFVKTMELVAEHGAAVVALTIDEQGQARTVEKKVEVAERLINDITSNWGVDKSAILIDCLTFTIATGQEESRKDGIETIDAIRELKKRHPAVQTTLGLSNISFGLNPSARQVLNSVFLHECQEAGLDSAIVHASKILPINRIPEEQRQAAL | ||||||
Domain | 642-735 | B12-binding N-terminal | ||||
Sequence: REAELAKLPLFDRLAQRIVDGERNGLDVDLDEAMTQKPPLAIINENLLDGMKTVGELFGSGQMQLPFVLQSAEVMKAAVAYLEPHMEKSDCDFG | ||||||
Domain | 740-877 | B12-binding | ||||
Sequence: KGRIVLATVKGDVHDIGKNLVDIILSNNGYEVVNLGIKQPITNILEVAEDKSADVVGMSGLLVKSTVIMKENLEEMNTRGVAEKFPVLLGGAALTRSYVENDLAEVYEGEVHYARDAFEGLKLMDTIMSAKRGEALAP | ||||||
Region | 873-925 | Disordered | ||||
Sequence: EALAPGSPESLAAEADRNKETERKARHERSKRIAVQRKAAEEPVEVPERSDVP | ||||||
Compositional bias | 885-924 | Basic and acidic residues | ||||
Sequence: AEADRNKETERKARHERSKRIAVQRKAAEEPVEVPERSDV | ||||||
Domain | 907-1206 | AdoMet activation | ||||
Sequence: VQRKAAEEPVEVPERSDVPSDVEVPAPPFWGSRIIKGLAVADYTGFLDERALFLGQWGLRGVRGGAGPSYEDLVQTEGRPRLRYWLDRLSTYGVLAYAAVVYGYFPAVSEDNDIVVLAEPRPDAEQRYRFTFPRQQRGRFLCIADFIRSRDLATERSEVDVLPFQLVTMGQPIADFVGELFVSNSYRDYLEVHGIGVQLTEALAEYWHRRIREELKFSGNRTMSADDPEAVEDYFKLGYRGARFAFGYGACPDLEDRIKMMELLQPERIGVTISEELQLHPEQSTDAFVLHHPAAKYFNV |
Domain
Modular enzyme with four functionally distinct domains. The isolated Hcy-binding domain catalyzes methyl transfer from free methylcobalamin to homocysteine. The Hcy-binding domain in association with the pterin-binding domain catalyzes the methylation of cob(I)alamin by methyltetrahydrofolate and the methylation of homocysteine. The B12-binding domain binds the cofactor. The AdoMet activation domain binds S-adenosyl-L-methionine. Under aerobic conditions cob(I)alamin can be converted to inactive cob(II)alamin. Reductive methylation by S-adenosyl-L-methionine and flavodoxin regenerates methylcobalamin (By similarity).
Sequence similarities
Belongs to the vitamin-B12 dependent methionine synthase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,206
- Mass (Da)132,392
- Last updated2001-04-27 v3
- Checksum7786CE5307D7CA86
Sequence caution
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 885-924 | Basic and acidic residues | ||||
Sequence: AEADRNKETERKARHERSKRIAVQRKAAEEPVEVPERSDV |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U00017 EMBL· GenBank· DDBJ | AAA17182.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AL035310 EMBL· GenBank· DDBJ | CAA22918.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AL583921 EMBL· GenBank· DDBJ | CAC31688.1 EMBL· GenBank· DDBJ | Genomic DNA |