Identification
Name:Methionine synthase
Synonyms:
  • 5-methyltetrahydrofolate--homocysteine methyltransferase
  • Methionine synthase, vitamin-B12-dependent
  • MS
Gene Name:metH
Enzyme Class:
Biological Properties
General Function:Involved in methionine synthase activity
Specific 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
Cellular Location:Not Available
SMPDB Pathways:
KEGG Pathways:
KEGG Reactions:
1.0Thumb+1.0Thumb1.0Thumb+1.0Thumb+1.0Thumb
1.0Thumb+1.0Thumb1.0Thumb+1.0Thumb
SMPDB Reactions:
1.05-Methyltetrahydrofolic acid+1.0Homocysteine+1.0Thumb+1.0Thumb1.0Tetrahydrofolic acid+1.0Thumb+1.0Thumb
1.05-Methyltetrahydrofolic acid + 1.0Homocysteine + 1.05-Methyltetrahydrofolic acid + 1.0Homocysteine → 1.0Tetrahydrofolic acid + 1.0L-Methionine + 1.0Tetrahydrofolic acid
ReactionCard
1.0Homocysteine+1.0Thumb+1.0Thumb1.0Thumb+1.0Thumb
1.0Homocysteine+1.0Thumb+1.0Thumb1.0Thumb+1.0Thumb
EcoCyc Reactions:
1.0Thumb+1.0Thumb1.0Thumb+1.0Thumb+1.0Thumb
1.0Thumb+1.0Thumb ? 1.0Thumb+1.0Thumb
Complex Reactions:
1.0Thumb+1.0Thumb1.0Thumb+1.0Thumb
Metabolites:
ECMDB IDNameView
ECMDB24199 N5-methyl--tetrahydropteroyl tri-L-glutamateMetaboCard
ECMDB013965-Methyltetrahydrofolic acidMetaboCard
ECMDB010795-Methyltetrahydropteroyltri-L-glutamic acidMetaboCard
ECMDB24053HomocysteineMetaboCard
ECMDB21225Hydrogen ionMetaboCard
ECMDB00165L-HomocysteineMetaboCard
ECMDB00696L-MethionineMetaboCard
ECMDB24244N5-methyl--tetrahydropteroyl tri-L-glutamateMetaboCard
ECMDB21010SelenohomocysteineMetaboCard
ECMDB01846Tetrahydrofolic acidMetaboCard
ECMDB23160tetrahydropteroyltri-L-glutamateMetaboCard
ECMDB01174Tetrahydropteroyltri-L-glutamic acidMetaboCard
GO Classification:
Component
cell part
intracellular
Function
binding
catalytic activity
cation binding
cobalamin binding
homocysteine S-methyltransferase activity
ion binding
metal ion binding
methionine synthase activity
methyltransferase activity
S-methyltransferase activity
transferase activity
transferase activity, transferring one-carbon groups
transition metal ion binding
vitamin binding
zinc ion binding
Process
cellular amino acid and derivative metabolic process
cellular amino acid metabolic process
cellular aromatic compound metabolic process
cellular metabolic process
metabolic process
methionine biosynthetic process
pteridine and derivative metabolic process
sulfur amino acid biosynthetic process
sulfur amino acid metabolic process
Gene Properties
Blattner:b4019
Gene OrientationClockwise
Centisome Percentage:90.99
Left Sequence End4221851
Right Sequence End4225534
Gene Sequence:
>3684 bp
GTGAGCAGCAAAGTGGAACAACTGCGTGCGCAGTTAAATGAACGTATTCTGGTGCTGGAC
GGCGGTATGGGCACCATGATCCAGAGTTATCGACTGAACGAAGCCGATTTTCGTGGTGAA
CGCTTTGCCGACTGGCCATGCGACCTCAAAGGCAACAACGACCTGCTGGTACTCAGTAAA
CCGGAAGTGATCGCCGCTATCCACAACGCCTACTTTGAAGCGGGCGCGGATATCATCGAA
ACCAACACCTTCAACTCCACGACCATTGCGATGGCGGATTACCAGATGGAATCCCTGTCG
GCGGAAATCAACTTTGCGGCGGCGAAACTGGCGCGAGCTTGTGCTGACGAGTGGACCGCG
CGCACGCCAGAGAAACCGCGCTACGTTGCCGGTGTTCTCGGCCCGACCAACCGCACGGCG
TCTATTTCTCCGGACGTCAACGATCCGGCATTTCGTAATATCACTTTTGACGGGCTGGTG
GCGGCTTATCGAGAGTCCACCAAAGCGCTGGTGGAAGGTGGCGCGGATCTGATCCTGATT
GAAACCGTTTTCGACACCCTTAACGCCAAAGCGGCGGTATTTGCGGTGAAAACGGAGTTT
GAAGCGCTGGGCGTTGAGCTGCCGATTATGATCTCCGGCACCATCACCGACGCCTCCGGG
CGCACGCTCTCCGGGCAGACCACCGAAGCATTTTACAACTCATTGCGCCACGCCGAAGCT
CTGACCTTTGGCCTGAACTGTGCGCTGGGGCCCGATGAACTGCGCCAGTACGTGCAGGAG
CTGTCACGGATTGCGGAATGCTACGTCACCGCGCACCCGAACGCCGGGCTACCCAACGCC
TTTGGTGAGTACGATCTCGACGCCGACACGATGGCAAAACAGATACGTGAATGGGCGCAA
GCGGGTTTTCTCAATATCGTCGGCGGCTGCTGTGGCACCACGCCACAACATATTGCAGCG
ATGAGTCGTGCAGTAGAAGGATTAGCGCCGCGCAAACTGCCGGAAATTCCCGTAGCCTGC
CGTTTGTCCGGCCTGGAGCCGCTGAACATTGGCGAAGATAGCCTGTTTGTGAACGTGGGT
GAACGCACCAACGTCACCGGTTCCGCTAAGTTCAAGCGCCTGATCAAAGAAGAGAAATAC
AGCGAGGCGCTGGATGTCGCGCGTCAACAGGTGGAAAACGGCGCGCAGATTATCGATATC
AACATGGATGAAGGGATGCTCGATGCCGAAGCGGCGATGGTGCGTTTTCTCAATCTGATT
GCCGGTGAACCGGATATCGCTCGCGTGCCGATTATGATCGACTCCTCAAAATGGGACGTC
ATTGAAAAAGGTCTGAAGTGTATCCAGGGCAAAGGCATTGTTAACTCTATCTCGATGAAA
GAGGGCGTCGATGCCTTTATCCATCACGCGAAATTGTTGCGTCGCTACGGTGCGGCAGTG
GTGGTAATGGCCTTTGACGAACAGGGACAGGCCGATACTCGCGCACGGAAAATCGAGATT
TGCCGTCGGGCGTACAAAATCCTCACCGAAGAGGTTGGCTTCCCGCCAGAAGATATCATC
TTCGACCCAAACATCTTCGCGGTCGCAACTGGCATTGAAGAGCACAACAACTACGCGCAG
GACTTTATCGGCGCGTGTGAAGACATCAAACGCGAACTGCCGCACGCGCTGATTTCCGGC
GGCGTATCTAACGTTTCTTTCTCGTTCCGTGGCAACGATCCGGTGCGCGAAGCCATTCAC
GCAGTGTTCCTCTACTACGCTATTCGCAATGGCATGGATATGGGGATCGTCAACGCCGGG
CAACTGGCGATTTACGACGACCTACCCGCTGAACTGCGCGACGCGGTGGAAGATGTGATT
CTTAATCGTCGCGACGATGGCACCGAGCGTTTACTGGAGCTTGCCGAGAAATATCGCGGC
AGCAAAACCGACGACACCGCCAACGCCCAGCAGGCGGAGTGGCGCTCGTGGGAAGTGAAT
AAACGTCTGGAATACTCGCTGGTCAAAGGCATTACCGAGTTTATCGAGCAGGATACCGAA
GAAGCCCGCCAGCAGGCTACGCGCCCGATTGAAGTGATTGAAGGCCCGTTGATGGACGGC
ATGAATGTGGTCGGCGACCTGTTTGGCGAAGGGAAAATGTTCCTGCCACAGGTGGTCAAA
TCGGCGCGCGTCATGAAACAGGCGGTGGCCTACCTCGAACCGTTTATTGAAGCCAGCAAA
GAGCAGGGCAAAACCAACGGCAAGATGGTGATCGCCACCGTGAAGGGCGACGTCCACGAC
ATCGGTAAAAATATCGTTGGTGTGGTGCTGCAATGTAACAACTACGAAATTGTCGATCTC
GGCGTTATGGTGCCTGCGGAAAAAATTCTCCGTACCGCTAAAGAAGTGAATGCTGATCTG
ATTGGCCTTTCGGGGCTTATCACGCCGTCGCTGGACGAGATGGTTAACGTGGCGAAAGAG
ATGGAGCGTCAGGGCTTCACTATTCCGTTACTGATTGGCGGCGCGACGACCTCAAAAGCG
CACACGGCGGTGAAAATCGAGCAGAACTACAGCGGCCCGACGGTGTATGTGCAGAATGCC
TCGCGTACCGTTGGTGTGGTGGCGGCGCTGCTTTCCGATACCCAGCGTGATGATTTTGTC
GCTCGTACCCGCAAGGAGTACGAAACCGTACGTATTCAGCACGGGCGCAAGAAACCGCGC
ACACCACCGGTCACGCTGGAAGCGGCGCGCGATAACGATTTCGCTTTTGACTGGCAGGCT
TACACGCCGCCGGTGGCGCACCGTCTCGGCGTGCAGGAAGTCGAAGCCAGCATCGAAACG
CTGCGTAATTACATCGACTGGACACCGTTCTTTATGACCTGGTCGCTGGCCGGGAAGTAT
CCGCGCATTCTGGAAGATGAAGTGGTGGGCGTTGAGGCGCAGCGGCTGTTTAAAGACGCC
AACGACATGCTGGATAAATTAAGCGCCGAGAAAACGCTGAATCCGCGTGGCGTGGTGGGC
CTGTTCCCGGCAAACCGTGTGGGCGATGACATTGAAATCTACCGTGACGAAACGCGTACC
CATGTGATCAACGTCAGCCACCATCTGCGTCAACAGACCGAAAAAACAGGCTTCGCTAAC
TACTGTCTCGCTGACTTCGTTGCGCCGAAGCTTTCTGGTAAAGCAGATTACATCGGCGCA
TTTGCCGTGACTGGCGGGCTGGAAGAGGACGCACTGGCTGATGCCTTTGAAGCGCAGCAC
GATGATTACAACAAAATCATGGTGAAAGCGCTTGCCGACCGTTTAGCCGAAGCCTTTGCG
GAGTATCTCCATGAGCGTGTGCGTAAAGTCTACTGGGGCTATGCGCCGAACGAGAACCTC
AGCAACGAAGAGCTGATCCGCGAAAACTACCAGGGCATCCGTCCGGCACCGGGCTATCCG
GCCTGCCCGGAACATACGGAAAAAGCCACCATCTGGGAGCTGCTGGAAGTGGAAAAACAC
ACTGGCATGAAACTCACAGAATCTTTCGCCATGTGGCCCGGTGCATCGGTTTCGGGTTGG
TACTTCAGCCACCCGGACAGCAAGTACTACGCTGTAGCACAAATTCAGCGCGATCAGGTT
GAAGATTATGCCCGCCGTAAAGGTATGAGCGTTACCGAAGTTGAGCGCTGGCTGGCACCG
AATCTGGGGTATGACGCGGACTGA
Protein Properties
Pfam Domain Function:
Protein Residues:1227
Protein Molecular Weight:135996
Protein Theoretical pI:5
PDB File:1K98
Signaling Regions:
  • None
Transmembrane Regions:
  • None
Protein Sequence:
>Methionine synthase
MSSKVEQLRAQLNERILVLDGGMGTMIQSYRLNEADFRGERFADWPCDLKGNNDLLVLSK
PEVIAAIHNAYFEAGADIIETNTFNSTTIAMADYQMESLSAEINFAAAKLARACADEWTA
RTPEKPRYVAGVLGPTNRTASISPDVNDPAFRNITFDGLVAAYRESTKALVEGGADLILI
ETVFDTLNAKAAVFAVKTEFEALGVELPIMISGTITDASGRTLSGQTTEAFYNSLRHAEA
LTFGLNCALGPDELRQYVQELSRIAECYVTAHPNAGLPNAFGEYDLDADTMAKQIREWAQ
AGFLNIVGGCCGTTPQHIAAMSRAVEGLAPRKLPEIPVACRLSGLEPLNIGEDSLFVNVG
ERTNVTGSAKFKRLIKEEKYSEALDVARQQVENGAQIIDINMDEGMLDAEAAMVRFLNLI
AGEPDIARVPIMIDSSKWDVIEKGLKCIQGKGIVNSISMKEGVDAFIHHAKLLRRYGAAV
VVMAFDEQGQADTRARKIEICRRAYKILTEEVGFPPEDIIFDPNIFAVATGIEEHNNYAQ
DFIGACEDIKRELPHALISGGVSNVSFSFRGNDPVREAIHAVFLYYAIRNGMDMGIVNAG
QLAIYDDLPAELRDAVEDVILNRRDDGTERLLELAEKYRGSKTDDTANAQQAEWRSWEVN
KRLEYSLVKGITEFIEQDTEEARQQATRPIEVIEGPLMDGMNVVGDLFGEGKMFLPQVVK
SARVMKQAVAYLEPFIEASKEQGKTNGKMVIATVKGDVHDIGKNIVGVVLQCNNYEIVDL
GVMVPAEKILRTAKEVNADLIGLSGLITPSLDEMVNVAKEMERQGFTIPLLIGGATTSKA
HTAVKIEQNYSGPTVYVQNASRTVGVVAALLSDTQRDDFVARTRKEYETVRIQHGRKKPR
TPPVTLEAARDNDFAFDWQAYTPPVAHRLGVQEVEASIETLRNYIDWTPFFMTWSLAGKY
PRILEDEVVGVEAQRLFKDANDMLDKLSAEKTLNPRGVVGLFPANRVGDDIEIYRDETRT
HVINVSHHLRQQTEKTGFANYCLADFVAPKLSGKADYIGAFAVTGGLEEDALADAFEAQH
DDYNKIMVKALADRLAEAFAEYLHERVRKVYWGYAPNENLSNEELIRENYQGIRPAPGYP
ACPEHTEKATIWELLEVEKHTGMKLTESFAMWPGASVSGWYFSHPDSKYYAVAQIQRDQV
EDYARRKGMSVTEVERWLAPNLGYDAD
References
External Links:
ResourceLink
Uniprot ID:P13009
Uniprot Name:METH_ECOLI
GenBank Gene ID:AP009048
Genebank Protein ID:85676771
PDB ID:1K98
Ecogene ID:EG10587
Ecocyc:EG10587
ColiBase:b4019
Kegg Gene:b4019
EchoBASE ID:EB0582
CCDB:METH_ECOLI
BacMap:16131845
General Reference:
  • Bandarian, V., Pattridge, K. A., Lennon, B. W., Huddler, D. P., Matthews, R. G., Ludwig, M. L. (2002). "Domain alternation switches B(12)-dependent methionine synthase to the activation conformation." Nat Struct Biol 9:53-56. Pubmed: 11731805
  • Banerjee, R. V., Johnston, N. L., Sobeski, J. K., Datta, P., Matthews, R. G. (1989). "Cloning and sequence analysis of the Escherichia coli metH gene encoding cobalamin-dependent methionine synthase and isolation of a tryptic fragment containing the cobalamin-binding domain." J Biol Chem 264:13888-13895. Pubmed: 2668277
  • Blattner, F. R., Burland, V., Plunkett, G. 3rd, Sofia, H. J., Daniels, D. L. (1993). "Analysis of the Escherichia coli genome. IV. DNA sequence of the region from 89.2 to 92.8 minutes." Nucleic Acids Res 21:5408-5417. Pubmed: 8265357
  • Blattner, F. R., Plunkett, G. 3rd, Bloch, C. A., Perna, N. T., Burland, V., Riley, M., Collado-Vides, J., Glasner, J. D., Rode, C. K., Mayhew, G. F., Gregor, J., Davis, N. W., Kirkpatrick, H. A., Goeden, M. A., Rose, D. J., Mau, B., Shao, Y. (1997). "The complete genome sequence of Escherichia coli K-12." Science 277:1453-1462. Pubmed: 9278503
  • Dixon, M. M., Huang, S., Matthews, R. G., Ludwig, M. (1996). "The structure of the C-terminal domain of methionine synthase: presenting S-adenosylmethionine for reductive methylation of B12." Structure 4:1263-1275. Pubmed: 8939751
  • Drennan, C. L., Huang, S., Drummond, J. T., Matthews, R. G., Lidwig, M. L. (1994). "How a protein binds B12: A 3.0 A X-ray structure of B12-binding domains of methionine synthase." Science 266:1669-1674. Pubmed: 7992050
  • Drummond, J. T., Loo, R. R., Matthews, R. G. (1993). "Electrospray mass spectrometric analysis of the domains of a large enzyme: observation of the occupied cobalamin-binding domain and redefinition of the carboxyl terminus of methionine synthase." Biochemistry 32:9282-9289. Pubmed: 8369296
  • Goulding, C. W., Matthews, R. G. (1997). "Cobalamin-dependent methionine synthase from Escherichia coli: involvement of zinc in homocysteine activation." Biochemistry 36:15749-15757. Pubmed: 9398304
  • Goulding, C. W., Postigo, D., Matthews, R. G. (1997). "Cobalamin-dependent methionine synthase is a modular protein with distinct regions for binding homocysteine, methyltetrahydrofolate, cobalamin, and adenosylmethionine." Biochemistry 36:8082-8091. Pubmed: 9201956
  • Hayashi, K., Morooka, N., Yamamoto, Y., Fujita, K., Isono, K., Choi, S., Ohtsubo, E., Baba, T., Wanner, B. L., Mori, H., Horiuchi, T. (2006). "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Mol Syst Biol 2:2006.0007. Pubmed: 16738553
  • Jarrett, J. T., Amaratunga, M., Drennan, C. L., Scholten, J. D., Sands, R. H., Ludwig, M. L., Matthews, R. G. (1996). "Mutations in the B12-binding region of methionine synthase: how the protein controls methylcobalamin reactivity." Biochemistry 35:2464-2475. Pubmed: 8652590
  • Luschinsky, C. L., Drummond, J. T., Matthews, R. G., Ludwig, M. L. (1992). "Crystallization and preliminary X-ray diffraction studies of the cobalamin-binding domain of methionine synthase from Escherichia coli." J Mol Biol 225:557-560. Pubmed: 1593636
  • Matthews, R. G. (2001). "Cobalamin-dependent methyltransferases." Acc Chem Res 34:681-689. Pubmed: 11513576
  • Old, I. G., Margarita, D., Glass, R. E., Saint Girons, I. (1990). "Nucleotide sequence of the metH gene of Escherichia coli K-12 and comparison with that of Salmonella typhimurium LT2." Gene 87:15-21. Pubmed: 2185137
  • Peariso, K., Zhou, Z. S., Smith, A. E., Matthews, R. G., Penner-Hahn, J. E. (2001). "Characterization of the zinc sites in cobalamin-independent and cobalamin-dependent methionine synthase using zinc and selenium X-ray absorption spectroscopy." Biochemistry 40:987-993. Pubmed: 11170420