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P13009 (METH_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Methionine synthase

EC=2.1.1.13
Alternative name(s):
5-methyltetrahydrofolate--homocysteine methyltransferase
Methionine synthase, vitamin-B12-dependent
Short name=MS
Gene names
Name:metH
Ordered Locus Names:b4019, JW3979
OrganismEscherichia coli (strain K12) [Reference proteome] [HAMAP]
Taxonomic identifier83333 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia

Protein attributes

Sequence length1227 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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.

Catalytic activity

5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine.

Cofactor

Methylcobalamin (MeCBL).

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.

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. Ref.7

Miscellaneous

L-homocysteine is bound via the zinc atom.

Sequence similarities

Belongs to the vitamin-B12 dependent methionine synthase family.

Contains 1 AdoMet activation domain.

Contains 1 B12-binding domain.

Contains 1 B12-binding N-terminal domain.

Contains 1 Hcy-binding domain.

Contains 1 pterin-binding domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.7
Chain2 – 12271226Methionine synthase
PRO_0000204532

Regions

Domain2 – 325324Hcy-binding
Domain356 – 617262Pterin-binding
Domain650 – 74495B12-binding N-terminal
Domain746 – 881136B12-binding
Domain897 – 1227331AdoMet activation
Region834 – 8352Cobalamin-binding
Region1189 – 11902S-adenosyl-L-methionine binding

Sites

Metal binding2471Zinc
Metal binding3101Zinc
Metal binding3111Zinc
Metal binding7591Cobalt (cobalamin axial ligand) Ref.14
Binding site8041Cobalamin
Binding site9461S-adenosyl-L-methionine
Binding site11341S-adenosyl-L-methionine; via carbonyl oxygen
Binding site11381Cobalamin; via carbonyl oxygen

Experimental info

Mutagenesis3101C → A or S: Loss of zinc binding. Loss of catalytic activity. Ref.7
Mutagenesis3111C → A or S: Loss of zinc binding. Loss of catalytic activity. Ref.7
Mutagenesis7571D → E: Decreases activity by about 70%. Ref.9
Mutagenesis7571D → N: Decreases activity by about 45%. Ref.9
Mutagenesis7591H → G: Loss of catalytic activity. Ref.9
Mutagenesis8101S → A: Decreases activity by about 40%. Ref.9
Sequence conflict1131A → R Ref.1
Sequence conflict1131A → R Ref.2
Sequence conflict6411S → T Ref.1
Sequence conflict6411S → T Ref.2
Sequence conflict1079 – 10802QH → HD in CAA34601. Ref.1
Sequence conflict1195 – 122733IQRDQ…GYDAD → TSARSG in CAA34601. Ref.1

Secondary structure

................................................................................................. 1227
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P13009 [UniParc].

Last modified January 23, 2007. Version 5.
Checksum: 91F0CAA1E9127D9A

FASTA1,227135,997
        10         20         30         40         50         60 
MSSKVEQLRA QLNERILVLD GGMGTMIQSY RLNEADFRGE RFADWPCDLK GNNDLLVLSK 

        70         80         90        100        110        120 
PEVIAAIHNA YFEAGADIIE TNTFNSTTIA MADYQMESLS AEINFAAAKL ARACADEWTA 

       130        140        150        160        170        180 
RTPEKPRYVA GVLGPTNRTA SISPDVNDPA FRNITFDGLV AAYRESTKAL VEGGADLILI 

       190        200        210        220        230        240 
ETVFDTLNAK AAVFAVKTEF EALGVELPIM ISGTITDASG RTLSGQTTEA FYNSLRHAEA 

       250        260        270        280        290        300 
LTFGLNCALG PDELRQYVQE LSRIAECYVT AHPNAGLPNA FGEYDLDADT MAKQIREWAQ 

       310        320        330        340        350        360 
AGFLNIVGGC CGTTPQHIAA MSRAVEGLAP RKLPEIPVAC RLSGLEPLNI GEDSLFVNVG 

       370        380        390        400        410        420 
ERTNVTGSAK FKRLIKEEKY SEALDVARQQ VENGAQIIDI NMDEGMLDAE AAMVRFLNLI 

       430        440        450        460        470        480 
AGEPDIARVP IMIDSSKWDV IEKGLKCIQG KGIVNSISMK EGVDAFIHHA KLLRRYGAAV 

       490        500        510        520        530        540 
VVMAFDEQGQ ADTRARKIEI CRRAYKILTE EVGFPPEDII FDPNIFAVAT GIEEHNNYAQ 

       550        560        570        580        590        600 
DFIGACEDIK RELPHALISG GVSNVSFSFR GNDPVREAIH AVFLYYAIRN GMDMGIVNAG 

       610        620        630        640        650        660 
QLAIYDDLPA ELRDAVEDVI LNRRDDGTER LLELAEKYRG SKTDDTANAQ QAEWRSWEVN 

       670        680        690        700        710        720 
KRLEYSLVKG ITEFIEQDTE EARQQATRPI EVIEGPLMDG MNVVGDLFGE GKMFLPQVVK 

       730        740        750        760        770        780 
SARVMKQAVA YLEPFIEASK EQGKTNGKMV IATVKGDVHD IGKNIVGVVL QCNNYEIVDL 

       790        800        810        820        830        840 
GVMVPAEKIL RTAKEVNADL IGLSGLITPS LDEMVNVAKE MERQGFTIPL LIGGATTSKA 

       850        860        870        880        890        900 
HTAVKIEQNY SGPTVYVQNA SRTVGVVAAL LSDTQRDDFV ARTRKEYETV RIQHGRKKPR 

       910        920        930        940        950        960 
TPPVTLEAAR DNDFAFDWQA YTPPVAHRLG VQEVEASIET LRNYIDWTPF FMTWSLAGKY 

       970        980        990       1000       1010       1020 
PRILEDEVVG VEAQRLFKDA NDMLDKLSAE KTLNPRGVVG LFPANRVGDD IEIYRDETRT 

      1030       1040       1050       1060       1070       1080 
HVINVSHHLR QQTEKTGFAN YCLADFVAPK LSGKADYIGA FAVTGGLEED ALADAFEAQH 

      1090       1100       1110       1120       1130       1140 
DDYNKIMVKA LADRLAEAFA EYLHERVRKV YWGYAPNENL SNEELIRENY QGIRPAPGYP 

      1150       1160       1170       1180       1190       1200 
ACPEHTEKAT IWELLEVEKH TGMKLTESFA MWPGASVSGW YFSHPDSKYY AVAQIQRDQV 

      1210       1220 
EDYARRKGMS VTEVERWLAP NLGYDAD 

« Hide

References

« Hide 'large scale' references
[1]"Nucleotide sequence of the metH gene of Escherichia coli K-12 and comparison with that of Salmonella typhimurium LT2."
Old I.G., Margarita D., Glass R.E., Saint-Girons I.
Gene 87:15-21(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: K12.
[2]"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."
Banerjee R.V., Johnston N.L., Sobeski J.K., Datta P., Matthews R.G.
J. Biol. Chem. 264:13888-13895(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE.
Strain: K12.
[3]"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."
Drummond J.T., Loo R.R., Matthews R.G.
Biochemistry 32:9282-9289(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[4]"Analysis of the Escherichia coli genome. IV. DNA sequence of the region from 89.2 to 92.8 minutes."
Blattner F.R., Burland V.D., Plunkett G. III, Sofia H.J., Daniels D.L.
Nucleic Acids Res. 21:5408-5417(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / MG1655 / ATCC 47076.
[5]"The complete genome sequence of Escherichia coli K-12."
Blattner F.R., Plunkett G. III, 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.
Science 277:1453-1462(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / MG1655 / ATCC 47076.
[6]"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[7]"Cobalamin-dependent methionine synthase is a modular protein with distinct regions for binding homocysteine, methyltetrahydrofolate, cobalamin, and adenosylmethionine."
Goulding C.W., Postigo D., Matthews R.G.
Biochemistry 36:8082-8091(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-7, CHARACTERIZATION, DOMAIN, MUTAGENESIS OF CYS-310 AND CYS-311.
Strain: K12.
[8]"Crystallization and preliminary X-ray diffraction studies of the cobalamin-binding domain of methionine synthase from Escherichia coli."
Luschinsky C.L., Drummond J.T., Matthews R.G., Ludwig M.L.
J. Mol. Biol. 225:557-560(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: CRYSTALLIZATION.
[9]"Mutations in the B12-binding region of methionine synthase: how the protein controls methylcobalamin reactivity."
Jarrett J.T., Amaratunga M., Drennan C.L., Scholten J.D., Sands R.H., Ludwig M.L., Matthews R.G.
Biochemistry 35:2464-2475(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION, MUTAGENESIS OF ASP-757; HIS-759 AND SER-810.
Strain: K12.
[10]"Cobalamin-dependent methionine synthase from Escherichia coli: involvement of zinc in homocysteine activation."
Goulding C.W., Matthews R.G.
Biochemistry 36:15749-15757(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: ZINC BINDING SITES.
Strain: K12.
[11]"Escherichia coli proteome analysis using the gene-protein database."
VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C.
Electrophoresis 18:1243-1251(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY 2D-GEL.
[12]"Characterization of the zinc sites in cobalamin-independent and cobalamin-dependent methionine synthase using zinc and selenium X-ray absorption spectroscopy."
Peariso K., Zhou Z.S., Smith A.E., Matthews R.G., Penner-Hahn J.E.
Biochemistry 40:987-993(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: ZINC BINDING SITES, ROLE OF ZINC IN SUBSTRATE BINDING.
Strain: K12.
[13]"Cobalamin-dependent methyltransferases."
Matthews R.G.
Acc. Chem. Res. 34:681-689(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[14]"How a protein binds B12: a 3.0 A X-ray structure of B12-binding domains of methionine synthase."
Drennan C.L., Huang S., Drummond J.T., Matthews R.G., Ludwig M.L.
Science 266:1669-1674(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 651-896 IN COMPLEX WITH COBALAMIN.
[15]"The structure of the C-terminal domain of methionine synthase: presenting S-adenosylmethionine for reductive methylation of B12."
Dixon M.M., Huang S., Matthews R.G., Ludwig M.L.
Structure 4:1263-1275(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 897-1227 IN COMPLEX WITH S-ADENOSYL-L-METHIONINE.
Strain: K12.
[16]"Domain alternation switches B(12)-dependent methionine synthase to the activation conformation."
Bandarian V., Pattridge K.A., Lennon B.W., Huddler D.P., Matthews R.G., Ludwig M.L.
Nat. Struct. Biol. 9:53-56(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 651-1227 OF WILD-TYPE AND MUTANT GLY-759 IN COMPLEX WITH COBALAMIN.
Strain: K12.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X16584 Genomic DNA. Translation: CAA34601.1.
J04975 Unassigned DNA. Translation: AAA02995.1.
U00006 Genomic DNA. Translation: AAC43113.1.
U00096 Genomic DNA. Translation: AAC76989.1.
AP009048 Genomic DNA. Translation: BAE78021.1.
PIRXYECMH. B65209.
RefSeqNP_418443.1. NC_000913.3.
YP_492162.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1BMTX-ray3.00A/B651-896[»]
1K7YX-ray3.00A651-1227[»]
1K98X-ray3.75A651-1227[»]
1MSKX-ray1.80A897-1227[»]
3BULX-ray2.30A649-1227[»]
3IV9X-ray3.25A649-1227[»]
3IVAX-ray2.70A649-1227[»]
ProteinModelPortalP13009.
SMRP13009. Positions 12-1227.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP13009. 13 interactions.
STRING511145.b4019.

2D gel databases

SWISS-2DPAGEP13009.

Proteomic databases

PaxDbP13009.
PRIDEP13009.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAC76989; AAC76989; b4019.
BAE78021; BAE78021; BAE78021.
GeneID12934458.
948522.
KEGGecj:Y75_p3906.
eco:b4019.
PATRIC32123567. VBIEscCol129921_4132.

Organism-specific databases

EchoBASEEB0582.
EcoGeneEG10587. metH.

Phylogenomic databases

eggNOGCOG1410.
HOGENOMHOG000251409.
KOK00548.
OMASMKEGEA.
OrthoDBEOG6091CH.
PhylomeDBP13009.
ProtClustDBPRK09490.

Enzyme and pathway databases

BioCycEcoCyc:HOMOCYSMETB12-MONOMER.
ECOL316407:JW3979-MONOMER.
MetaCyc:HOMOCYSMETB12-MONOMER.
UniPathwayUPA00051; UER00081.

Gene expression databases

GenevestigatorP13009.

Family and domain databases

Gene3D1.10.1240.10. 1 hit.
3.10.196.10. 1 hit.
3.20.20.20. 1 hit.
3.20.20.330. 1 hit.
3.40.50.280. 1 hit.
InterProIPR003759. Cbl-bd_cap.
IPR006158. Cobalamin-bd.
IPR011005. Dihydropteroate_synth-like.
IPR011822. MetH.
IPR000489. Pterin-binding.
IPR003726. S_MeTrfase.
IPR004223. VitB12-dep_Met_synth_activ_dom.
[Graphical view]
PfamPF02310. B12-binding. 1 hit.
PF02607. B12-binding_2. 1 hit.
PF02965. Met_synt_B12. 1 hit.
PF00809. Pterin_bind. 1 hit.
PF02574. S-methyl_trans. 1 hit.
[Graphical view]
PIRSFPIRSF000381. MetH. 1 hit.
SMARTSM01018. B12-binding_2. 1 hit.
[Graphical view]
SUPFAMSSF47644. SSF47644. 1 hit.
SSF51717. SSF51717. 1 hit.
SSF52242. SSF52242. 1 hit.
SSF56507. SSF56507. 1 hit.
SSF82282. SSF82282. 1 hit.
TIGRFAMsTIGR02082. metH. 1 hit.
PROSITEPS50974. ADOMET_ACTIVATION. 1 hit.
PS51332. B12_BINDING. 1 hit.
PS51337. B12_BINDING_NTER. 1 hit.
PS50970. HCY. 1 hit.
PS50972. PTERIN_BINDING. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP13009.
PROP13009.

Entry information

Entry nameMETH_ECOLI
AccessionPrimary (citable) accession number: P13009
Secondary accession number(s): Q2M6T5
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 150 of the entry and version 5 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

Escherichia coli

Escherichia coli (strain K12): entries and cross-references to EcoGene