ID METE_ECOLI Reviewed; 753 AA. AC P25665; Q2M8D4; DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 6. DT 24-JAN-2024, entry version 199. DE RecName: Full=5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase {ECO:0000255|HAMAP-Rule:MF_00172}; DE EC=2.1.1.14 {ECO:0000255|HAMAP-Rule:MF_00172}; DE AltName: Full=Cobalamin-independent methionine synthase {ECO:0000255|HAMAP-Rule:MF_00172}; DE AltName: Full=Methionine synthase, vitamin-B12 independent isozyme {ECO:0000255|HAMAP-Rule:MF_00172}; GN Name=metE {ECO:0000255|HAMAP-Rule:MF_00172}; GN OrderedLocusNames=b3829, JW3805; OS Escherichia coli (strain K12). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales; OC Enterobacteriaceae; Escherichia. OX NCBI_TaxID=83333; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE. RC STRAIN=K12 / DH5-alpha; RX PubMed=1339288; DOI=10.1021/bi00141a013; RA Gonzalez J.C., Banerjee R.V., Huang S., Sumner J.S., Matthews R.G.; RT "Comparison of cobalamin-independent and cobalamin-dependent methionine RT synthases from Escherichia coli: two solutions to the same chemical RT problem."; RL Biochemistry 31:6045-6056(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / MG1655 / ATCC 47076; RX PubMed=1379743; DOI=10.1126/science.1379743; RA Daniels D.L., Plunkett G. III, Burland V.D., Blattner F.R.; RT "Analysis of the Escherichia coli genome: DNA sequence of the region from RT 84.5 to 86.5 minutes."; RL Science 257:771-778(1992). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND SEQUENCE REVISION. RC STRAIN=K12 / MG1655 / ATCC 47076; RX PubMed=8346018; DOI=10.1093/nar/21.15.3391; RA Plunkett G. III, Burland V., Daniels D.L., Blattner F.R.; RT "Analysis of the Escherichia coli genome. III. DNA sequence of the region RT from 87.2 to 89.2 minutes."; RL Nucleic Acids Res. 21:3391-3398(1993). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND SEQUENCE REVISION TO 604 RP AND 658. RC STRAIN=K12 / MG1655 / ATCC 47076; RX PubMed=9278503; DOI=10.1126/science.277.5331.1453; RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., RA Shao Y.; RT "The complete genome sequence of Escherichia coli K-12."; RL Science 277:1453-1462(1997). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911; RX PubMed=16738553; DOI=10.1038/msb4100049; RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.; RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 RT and W3110."; RL Mol. Syst. Biol. 2:E1-E5(2006). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22. RX PubMed=2643109; DOI=10.1073/pnas.86.1.85; RA Maxon M.E., Redfield B., Cai X.-Y., Shoeman R., Fujita K., Fisher W., RA Stauffer G., Weissbach H., Brot N.; RT "Regulation of methionine synthesis in Escherichia coli: effect of the MetR RT protein on the expression of the metE and metR genes."; RL Proc. Natl. Acad. Sci. U.S.A. 86:85-89(1989). RN [7] RP PROTEIN SEQUENCE OF 2-13. RC STRAIN=K12 / EMG2; RX PubMed=9298646; DOI=10.1002/elps.1150180807; RA Link A.J., Robison K., Church G.M.; RT "Comparing the predicted and observed properties of proteins encoded in the RT genome of Escherichia coli K-12."; RL Electrophoresis 18:1259-1313(1997). RN [8] RP CHARACTERIZATION, AND MUTAGENESIS OF CYS-726. RX PubMed=8823155; DOI=10.1021/bi9615452; RA Gonzalez J.C., Peariso K., Penner-Hahn J.E., Matthews R.G.; RT "Cobalamin-independent methionine synthase from Escherichia coli: a zinc RT metalloenzyme."; RL Biochemistry 35:12228-12234(1996). RN [9] RP IDENTIFICATION BY 2D-GEL. RX PubMed=9298644; DOI=10.1002/elps.1150180805; RA VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C.; RT "Escherichia coli proteome analysis using the gene-protein database."; RL Electrophoresis 18:1243-1251(1997). RN [10] RP MUTAGENESIS OF HIS-641; CYS-643 AND CYS-726. RX PubMed=10625458; DOI=10.1021/bi992062b; RA Zhou Z.S., Peariso K., Penner-Hahn J.E., Matthews R.G.; RT "Identification of the zinc ligands in cobalamin-independent methionine RT synthase (MetE) from Escherichia coli."; RL Biochemistry 38:15915-15926(1999). CC -!- FUNCTION: Catalyzes the transfer of a methyl group from 5- CC methyltetrahydrofolate to homocysteine resulting in methionine CC formation. {ECO:0000255|HAMAP-Rule:MF_00172}. CC -!- CATALYTIC ACTIVITY: CC Reaction=5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = L- CC methionine + tetrahydropteroyltri-L-glutamate; Xref=Rhea:RHEA:21196, CC ChEBI:CHEBI:57844, ChEBI:CHEBI:58140, ChEBI:CHEBI:58199, CC ChEBI:CHEBI:58207; EC=2.1.1.14; Evidence={ECO:0000255|HAMAP- CC Rule:MF_00172}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000255|HAMAP- CC Rule:MF_00172}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_00172}; CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo CC pathway; L-methionine from L-homocysteine (MetE route): step 1/1. CC {ECO:0000255|HAMAP-Rule:MF_00172}. CC -!- SUBUNIT: Monomer. CC -!- INTERACTION: CC P25665; P03018: uvrD; NbExp=2; IntAct=EBI-551247, EBI-559573; CC -!- MISCELLANEOUS: Has an absolute requirement for a polyglutamylated CC folate as substrate. Its activity depends on phosphate anions and CC divalent cations. CC -!- SIMILARITY: Belongs to the vitamin-B12 independent methionine synthase CC family. {ECO:0000255|HAMAP-Rule:MF_00172, ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M87625; AAA23544.1; -; Genomic_DNA. DR EMBL; M87049; AAA67625.1; -; Genomic_DNA. DR EMBL; U00096; AAC76832.1; -; Genomic_DNA. DR EMBL; AP009048; BAE77472.1; -; Genomic_DNA. DR EMBL; J04155; AAA24160.1; -; Genomic_DNA. DR PIR; F65187; A42863. DR RefSeq; NP_418273.1; NC_000913.3. DR RefSeq; WP_000153907.1; NZ_SSZK01000046.1. DR AlphaFoldDB; P25665; -. DR SMR; P25665; -. DR BioGRID; 4259477; 17. DR BioGRID; 852620; 1. DR DIP; DIP-6847N; -. DR IntAct; P25665; 12. DR STRING; 511145.b3829; -. DR jPOST; P25665; -. DR PaxDb; 511145-b3829; -. DR EnsemblBacteria; AAC76832; AAC76832; b3829. DR GeneID; 948323; -. DR KEGG; ecj:JW3805; -. DR KEGG; eco:b3829; -. DR PATRIC; fig|1411691.4.peg.2879; -. DR EchoBASE; EB0579; -. DR eggNOG; COG0620; Bacteria. DR HOGENOM; CLU_013175_0_0_6; -. DR InParanoid; P25665; -. DR OMA; KVMKGML; -. DR OrthoDB; 244285at2; -. DR PhylomeDB; P25665; -. DR BioCyc; EcoCyc:HOMOCYSMET-MONOMER; -. DR BioCyc; MetaCyc:HOMOCYSMET-MONOMER; -. DR BRENDA; 2.1.1.14; 2026. DR UniPathway; UPA00051; UER00082. DR PRO; PR:P25665; -. DR Proteomes; UP000000318; Chromosome. DR Proteomes; UP000000625; Chromosome. DR GO; GO:0005829; C:cytosol; IDA:EcoCyc. DR GO; GO:0003871; F:5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity; IDA:EcoCyc. DR GO; GO:0008705; F:methionine synthase activity; IDA:BHF-UCL. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0050667; P:homocysteine metabolic process; IDA:BHF-UCL. DR GO; GO:0009086; P:methionine biosynthetic process; IDA:BHF-UCL. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0035999; P:tetrahydrofolate interconversion; IDA:BHF-UCL. DR CDD; cd03311; CIMS_C_terminal_like; 1. DR CDD; cd03312; CIMS_N_terminal_like; 1. DR Gene3D; 3.20.20.210; -; 2. DR HAMAP; MF_00172; Meth_synth; 1. DR InterPro; IPR013215; Cbl-indep_Met_Synth_N. DR InterPro; IPR006276; Cobalamin-indep_Met_synthase. DR InterPro; IPR002629; Met_Synth_C/arc. DR InterPro; IPR038071; UROD/MetE-like_sf. DR NCBIfam; TIGR01371; met_syn_B12ind; 1. DR PANTHER; PTHR30519; 5-METHYLTETRAHYDROPTEROYLTRIGLUTAMATE--HOMOCYSTEINE METHYLTRANSFERASE; 1. DR PANTHER; PTHR30519:SF0; 5-METHYLTETRAHYDROPTEROYLTRIGLUTAMATE--HOMOCYSTEINE METHYLTRANSFERASE; 1. DR Pfam; PF08267; Meth_synt_1; 1. DR Pfam; PF01717; Meth_synt_2; 1. DR PIRSF; PIRSF000382; MeTrfase_B12_ind; 1. DR SUPFAM; SSF51726; UROD/MetE-like; 2. PE 1: Evidence at protein level; KW Amino-acid biosynthesis; Direct protein sequencing; Metal-binding; KW Methionine biosynthesis; Methyltransferase; Reference proteome; Repeat; KW Transferase; Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:9298646" FT CHAIN 2..753 FT /note="5-methyltetrahydropteroyltriglutamate--homocysteine FT methyltransferase" FT /id="PRO_0000098630" FT ACT_SITE 694 FT /note="Proton donor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT BINDING 17..20 FT /ligand="5-methyltetrahydropteroyltri-L-glutamate" FT /ligand_id="ChEBI:CHEBI:58207" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT BINDING 117 FT /ligand="5-methyltetrahydropteroyltri-L-glutamate" FT /ligand_id="ChEBI:CHEBI:58207" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT BINDING 431..433 FT /ligand="L-homocysteine" FT /ligand_id="ChEBI:CHEBI:58199" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT BINDING 431..433 FT /ligand="L-methionine" FT /ligand_id="ChEBI:CHEBI:57844" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT BINDING 484 FT /ligand="L-homocysteine" FT /ligand_id="ChEBI:CHEBI:58199" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT BINDING 484 FT /ligand="L-methionine" FT /ligand_id="ChEBI:CHEBI:57844" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT BINDING 515..516 FT /ligand="5-methyltetrahydropteroyltri-L-glutamate" FT /ligand_id="ChEBI:CHEBI:58207" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT BINDING 561 FT /ligand="5-methyltetrahydropteroyltri-L-glutamate" FT /ligand_id="ChEBI:CHEBI:58207" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT BINDING 599 FT /ligand="L-homocysteine" FT /ligand_id="ChEBI:CHEBI:58199" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT BINDING 599 FT /ligand="L-methionine" FT /ligand_id="ChEBI:CHEBI:57844" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT BINDING 605 FT /ligand="5-methyltetrahydropteroyltri-L-glutamate" FT /ligand_id="ChEBI:CHEBI:58207" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT BINDING 641 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT BINDING 643 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT BINDING 665 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT BINDING 726 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00172" FT MUTAGEN 641 FT /note="H->N: Impaired activity, lower affinity for zinc FT binding." FT /evidence="ECO:0000269|PubMed:10625458" FT MUTAGEN 641 FT /note="H->Q: Impaired activity, lower affinity for zinc FT binding. Binds homocysteine 2-4x more weakly than FT wild-type." FT /evidence="ECO:0000269|PubMed:10625458" FT MUTAGEN 643 FT /note="C->S: Impaired activity, lower affinity for zinc FT binding. Binds homocysteine 7x tighter than wild-type." FT /evidence="ECO:0000269|PubMed:10625458" FT MUTAGEN 726 FT /note="C->S: Impaired activity, lower affinity for zinc FT binding. Binds homocysteine 2-4x more weakly than FT wild-type." FT /evidence="ECO:0000269|PubMed:10625458, FT ECO:0000269|PubMed:8823155" FT CONFLICT 363 FT /note="L -> V (in Ref. 1; AAA23544)" FT /evidence="ECO:0000305" FT CONFLICT 605 FT /note="E -> Q (in Ref. 3; AAA67625)" FT /evidence="ECO:0000305" FT CONFLICT 659 FT /note="A -> R (in Ref. 3; AAA67625)" FT /evidence="ECO:0000305" SQ SEQUENCE 753 AA; 84674 MW; C46BE52F227AFAF1 CRC64; MTILNHTLGF PRVGLRRELK KAQESYWAGN STREELLAVG RELRARHWDQ QKQAGIDLLP VGDFAWYDHV LTTSLLLGNV PARHQNKDGS VDIDTLFRIG RGRAPTGEPA AAAEMTKWFN TNYHYMVPEF VKGQQFKLTW TQLLDEVDEA LALGHKVKPV LLGPVTWLWL GKVKGEQFDR LSLLNDILPV YQQVLAELAK RGIEWVQIDE PALVLELPQA WLDAYKPAYD ALQGQVKLLL TTYFEGVTPN LDTITALPVQ GLHVDLVHGK DDVAELHKRL PSDWLLSAGL INGRNVWRAD LTEKYAQIKD IVGKRDLWVA SSCSLLHSPI DLSVETRLDA EVKSWFAFAL QKCHELALLR DALNSGDTAA LAEWSAPIQA RRHSTRVHNP AVEKRLAAIT AQDSQRANVY EVRAEAQRAR FKLPAWPTTT IGSFPQTTEI RTLRLDFKKG NLDANNYRTG IAEHIKQAIV EQERLGLDVL VHGEAERNDM VEYFGEHLDG FVFTQNGWVQ SYGSRCVKPP IVIGDISRPA PITVEWAKYA QSLTDKPVKG MLTGPVTILC WSFPREDVSR ETIAKQIALA LRDEVADLEA AGIGIIQIDE PALREGLPLR RSDWDAYLQW GVEAFRINAA VAKDDTQIHT HMCYCEFNDI MDSIAALDAD VITIETSRSD MELLESFEEF DYPNEIGPGV YDIHSPNVPS VEWIEALLKK AAKRIPAERL WVNPDCGLKT RGWPETRAAL ANMVQAAQNL RRG //