ID SYM_ECOLI Reviewed; 677 AA. AC P00959; Q2MAW4; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 02-SEP-2026, entry version 235. DE RecName: Full=Methionine--tRNA ligase {ECO:0000305}; DE EC=6.1.1.10 {ECO:0000269|PubMed:216545, ECO:0000269|PubMed:367445, ECO:0000269|PubMed:4297674, ECO:0000269|PubMed:4581817, ECO:0000269|PubMed:7932711}; DE AltName: Full=Methionyl transfer RNA synthetase {ECO:0000303|PubMed:4297674}; DE AltName: Full=Methionyl-tRNA synthetase {ECO:0000303|PubMed:4581817}; DE Short=MTS {ECO:0000303|PubMed:6094501}; DE Short=MetRS {ECO:0000303|PubMed:7042987}; GN Name=metG {ECO:0000303|PubMed:6094501, ECO:0000303|PubMed:6756915}; GN OrderedLocusNames=b2114, JW2101; OS Escherichia coli (strain K12). OC Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria; OC Enterobacterales; Enterobacteriaceae; Escherichia. OX NCBI_TaxID=83333; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=6094501; DOI=10.1128/jb.160.3.1115-1122.1984; RA Dardel F., Fayat G., Blanquet S.; RT "Molecular cloning and primary structure of the Escherichia coli methionyl- RT tRNA synthetase gene."; RL J. Bacteriol. 160:1115-1122(1984). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TRANSCRIPTIONAL REGULATION. RC STRAIN=K12; RX PubMed=2259334; DOI=10.1007/bf00315804; RA Dardel F., Panvert M., Fayat G.; RT "Transcription and regulation of expression of the Escherichia coli RT methionyl-tRNA synthetase gene."; RL Mol. Gen. Genet. 223:121-133(1990). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / BHB2600; RA Richterich P., Lakey N., Gryan G., Jaehn L., Mintz L., Robison K., RA Church G.M.; RT "Automated multiplex sequencing of the E.coli genome."; RL Submitted (OCT-1993) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. 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 1-566, AND PARTIAL PROTEIN SEQUENCE. RX PubMed=6756915; RA Barker D.G., Ebel J.-P., Jakes R., Bruton C.J.; RT "Methionyl-tRNA synthetase from Escherichia coli. Primary structure of the RT active crystallised tryptic fragment."; RL Eur. J. Biochem. 127:449-457(1982). RN [7] RP PROTEIN SEQUENCE OF 2-17, AND SUBUNIT. RX PubMed=4605346; DOI=10.1016/0014-5793(74)80922-1; RA Koch G.L., Bruton C.J.; RT "The subunit structure of methionyl-tRNA synthetase from Escherichia RT coli."; RL FEBS Lett. 40:180-182(1974). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RC STRAIN=K12; RX PubMed=4297674; DOI=10.1111/j.1432-1033.1968.tb00196.x; RA Lemoine F., Waller J.P., van Rapenbusch R.; RT "Studies on methionyl transfer RNA synthetase. 1. Purification and some RT properties of methionyl transfer RNA synthetase from Escherichia coli RT K-12."; RL Eur. J. Biochem. 4:213-221(1968). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR. RX PubMed=4581817; DOI=10.1111/j.1432-1033.1973.tb02903.x; RA Blanquet S., Iwatsubo M., Waller J.P.; RT "The mechanism of action of methionyl-tRNA synthetase from Escherichia RT coli. 1. Fluorescence studies on tRNAMet binding as a function of ligands, RT ions and pH."; RL Eur. J. Biochem. 36:213-226(1973). RN [10] RP FUNCTION, AND CATALYTIC ACTIVITY. RC STRAIN=K12; RX PubMed=216545; DOI=10.1111/j.1432-1033.1978.tb12758.x; RA Ron E.Z., Falk A., Helberg D., Horowitz S., Zeevi M.; RT "Preferential charging of tRNA-Met-f in Escherichia coli K12."; RL Eur. J. Biochem. 92:389-395(1978). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND SUBUNIT. RX PubMed=367445; DOI=10.1016/0005-2795(79)90491-4; RA Posorske L.H., Cohn M., Yanagisawa N., Auld D.S.; RT "Methionyl-tRNA synthetase of Escherichia coli. A zinc metalloprotein."; RL Biochim. Biophys. Acta 576:128-133(1979). RN [12] RP FUNCTION IN EDITING NON-COGNATE AMINOACYL ADENYLATE, AND CATALYTIC RP ACTIVITY. RX PubMed=7024910; DOI=10.1093/nar/9.13.3105; RA Jakubowski H., Fersht A.R.; RT "Alternative pathways for editing non-cognate amino acids by aminoacyl-tRNA RT synthetases."; RL Nucleic Acids Res. 9:3105-3117(1981). RN [13] RP MAPPING OF SUBSTRATE-BINDING SITES. RX PubMed=1702021; DOI=10.1021/bi00487a029; RA Hountondji C., Schmitter J.-M., Beauvallet C., Blanquet S.; RT "Mapping of the active site of Escherichia coli methionyl-tRNA synthetase: RT identification of amino acid residues labeled by periodate-oxidized RT tRNA(fMet) molecules having modified lengths at the 3'-acceptor end."; RL Biochemistry 29:8190-8198(1990). RN [14] RP FUNCTION IN EDITING NON-COGNATE AMINOACYL ADENYLATE, CATALYTIC ACTIVITY, RP ACTIVITY REGULATION, AND DISRUPTION PHENOTYPE. RX PubMed=2191291; DOI=10.1073/pnas.87.12.4504; RA Jakubowski H.; RT "Proofreading in vivo: editing of homocysteine by methionyl-tRNA synthetase RT in Escherichia coli."; RL Proc. Natl. Acad. Sci. U.S.A. 87:4504-4508(1990). RN [15] RP MUTAGENESIS OF VAL-299; HIS-302 AND TRP-306. RX PubMed=1959615; DOI=10.1016/0014-5793(91)80879-8; RA Fourmy D., Mechulam Y., Brunie S., Blanquet S., Fayat G.; RT "Identification of residues involved in the binding of methionine by RT Escherichia coli methionyl-tRNA synthetase."; RL FEBS Lett. 292:259-263(1991). RN [16] RP COFACTOR, AND MUTAGENESIS OF CYS-146; CYS-149; CYS-159 AND CYS-162. RX PubMed=8515465; DOI=10.1006/jmbi.1993.1352; RA Fourmy D., Meinnel T., Mechulam Y., Blanquet S.; RT "Mapping of the zinc binding domain of Escherichia coli methionyl-tRNA RT synthetase."; RL J. Mol. Biol. 231:1068-1077(1993). RN [17] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MUTAGENESIS OF GLY-331; LYS-333; 334-MET--SER-337; MET-334; SER-335; RP SER-337; ARG-338 AND GLY-339. RX PubMed=7932711; DOI=10.1006/jmbi.1994.1601; RA Schmitt E., Meinnel T., Blanquet S., Mechulam Y.; RT "Methionyl-tRNA synthetase needs an intact and mobile 332KMSKS336 motif in RT catalysis of methionyl adenylate formation."; RL J. Mol. Biol. 242:566-576(1994). RN [18] 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 [19] RP REVIEW. RX PubMed=2126467; DOI=10.1016/0300-9084(90)90126-2; RA Meinnel T., Mechulam Y., Dardel F., Schmitter J.-M., Hountondji C., RA Brunie S., Dessen P., Fayat G., Blanquet S.; RT "Methionyl-tRNA synthetase from E. coli -- a review."; RL Biochimie 72:625-632(1990). RN [20] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS). RX PubMed=7042987; DOI=10.1016/0022-2836(82)90492-2; RA Zelwer C., Risler J.-L., Brunie S.; RT "Crystal structure of Escherichia coli methionyl-tRNA synthetase at 2.5-A RT resolution."; RL J. Mol. Biol. 155:63-81(1982). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH ATP. RX PubMed=2254937; DOI=10.1016/s0022-2836(05)80331-6; RA Brunie S., Zelwer C., Risler J.-L.; RT "Crystallographic study at 2.5-A resolution of the interaction of RT methionyl-tRNA synthetase from Escherichia coli with ATP."; RL J. Mol. Biol. 216:411-424(1990). RN [22] {ECO:0007744|PDB:1MEA, ECO:0007744|PDB:1MED} RP STRUCTURE BY NMR OF 139-164 IN COMPLEX WITH ZN(2+). RX PubMed=8515466; DOI=10.1006/jmbi.1993.1353; RA Fourmy D., Dardel F., Blanquet S.; RT "Methionyl-tRNA synthetase zinc binding domain. Three-dimensional structure RT and homology with rubredoxin and gag retroviral proteins."; RL J. Mol. Biol. 231:1078-1089(1993). RN [23] {ECO:0007744|PDB:1QQT} RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 1-553 IN COMPLEX WITH ZN(2+). RX PubMed=10600385; DOI=10.1006/jmbi.1999.3339; RA Mechulam Y., Schmitt E., Maveyraud L., Zelwer C., Nureki O., Yokoyama S., RA Konno M., Blanquet S.; RT "Crystal structure of Escherichia coli methionyl-tRNA synthetase highlights RT species-specific features."; RL J. Mol. Biol. 294:1287-1297(1999). RN [24] {ECO:0007744|PDB:1F4L} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1-552 IN COMPLEX WITH RP L-METHIONINE AND ZN(2+). RX PubMed=11243794; DOI=10.1006/jmbi.2001.4408; RA Serre L., Verdon G., Choinowski T., Hervouet N., Risler J.-L., Zelwer C.; RT "How methionyl-tRNA synthetase creates its amino acid recognition pocket RT upon L-methionine binding."; RL J. Mol. Biol. 306:863-876(2001). RN [25] {ECO:0007744|PDB:1P7P, ECO:0007744|PDB:1PFU, ECO:0007744|PDB:1PFV, ECO:0007744|PDB:1PFW, ECO:0007744|PDB:1PFY, ECO:0007744|PDB:1PG0, ECO:0007744|PDB:1PG2} RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 2-552 IN COMPLEXES WITH RP METHIONINE; METHIONINE ANALOGS; L-METHIONYL ADENYLATE; ADENOSINE AND RP ZN(2+), AND DOMAIN. RX PubMed=12946347; DOI=10.1016/s0022-2836(03)00917-3; RA Crepin T., Schmitt E., Mechulam Y., Sampson P.B., Vaughan M.D., Honek J.F., RA Blanquet S.; RT "Use of analogues of methionine and methionyl adenylate to sample RT conformational changes during catalysis in Escherichia coli methionyl-tRNA RT synthetase."; RL J. Mol. Biol. 332:59-72(2003). CC -!- FUNCTION: Catalyzes the attachment of L-methionine to tRNA(Met) CC (PubMed:216545, PubMed:367445, PubMed:4297674, PubMed:4581817, CC PubMed:7932711). Is required not only for elongation of protein CC synthesis but also for the initiation of all mRNA translation through CC initiator tRNA(fMet) aminoacylation (PubMed:216545, PubMed:4581817). CC MetRS can indeed attach methionine to tRNA(mMet), which supplies CC methionine for elongation of nascent peptides, and to tRNA(fMet), which CC supplies formylmethionine for initiation of peptide synthesis CC (PubMed:216545, PubMed:4581817). However, MetRS charges tRNA(fMet) with CC a greater efficiency than tRNA(mMet) in several strains of E.coli, CC suggesting a preference for initiation of new peptides (PubMed:216545). CC Cannot use D-methionine (PubMed:4297674). {ECO:0000269|PubMed:216545, CC ECO:0000269|PubMed:367445, ECO:0000269|PubMed:4297674, CC ECO:0000269|PubMed:4581817, ECO:0000269|PubMed:7932711}. CC -!- FUNCTION: In addition, MetRS can reject misactivated homocysteine by a CC tRNA-independent hydrolysis of the homocysteinyl-AMP intermediate, CC preventing incorporation of homocysteine into tRNA and proteins CC (PubMed:2191291, PubMed:7024910). The homocysteinyl-AMP intermediate CC undergoes an intramolecular cyclization reaction in which the thiolate CC side chain of homocysteine displaces the AMP group, forming CC homocysteine-thiolactone and AMP (PubMed:2191291, PubMed:7024910). CC {ECO:0000269|PubMed:2191291, ECO:0000269|PubMed:7024910}. CC -!- CATALYTIC ACTIVITY: CC Reaction=tRNA(Met) + L-methionine + ATP = L-methionyl-tRNA(Met) + AMP + CC diphosphate; Xref=Rhea:RHEA:13481, Rhea:RHEA-COMP:9667, Rhea:RHEA- CC COMP:9698, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57844, CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78530, ChEBI:CHEBI:456215; CC EC=6.1.1.10; Evidence={ECO:0000269|PubMed:216545, CC ECO:0000269|PubMed:367445, ECO:0000269|PubMed:4297674, CC ECO:0000269|PubMed:4581817, ECO:0000269|PubMed:7932711}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13482; CC Evidence={ECO:0000269|PubMed:216545, ECO:0000269|PubMed:367445, CC ECO:0000269|PubMed:4297674, ECO:0000269|PubMed:4581817, CC ECO:0000269|PubMed:7932711}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-homocysteine + ATP = L-homocysteine thiolactone + AMP + CC diphosphate; Xref=Rhea:RHEA:83875, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:58199, ChEBI:CHEBI:233452, CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:2191291, CC ECO:0000269|PubMed:7024910}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83876; CC Evidence={ECO:0000269|PubMed:2191291, ECO:0000269|PubMed:7024910}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-homocysteine + ATP + H(+) = L-homocysteinyl-AMP + CC diphosphate; Xref=Rhea:RHEA:83879, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58199, CC ChEBI:CHEBI:233461; Evidence={ECO:0000269|PubMed:2191291, CC ECO:0000269|PubMed:7024910}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83880; CC Evidence={ECO:0000269|PubMed:2191291, ECO:0000269|PubMed:7024910}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-homocysteinyl-AMP = L-homocysteine thiolactone + AMP + H(+); CC Xref=Rhea:RHEA:83883, ChEBI:CHEBI:15378, ChEBI:CHEBI:233452, CC ChEBI:CHEBI:233461, ChEBI:CHEBI:456215; CC Evidence={ECO:0000269|PubMed:2191291, ECO:0000269|PubMed:7024910}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83884; CC Evidence={ECO:0000269|PubMed:2191291, ECO:0000269|PubMed:7024910}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:367445, ECO:0000269|PubMed:8515465}; CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:4581817}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:367445, CC ECO:0000269|PubMed:8515465}; CC -!- ACTIVITY REGULATION: Inhibited by the metal chelator 1,10- CC phenanthroline, but not by its non-chelating structural isomers 1,7- CC phenanthroline and 4,7-phenanthroline (PubMed:367445). Synthesis of CC homocysteine thiolactone is inhibited by methionine and norleucine, an CC artificial substrate of the synthetase (PubMed:2191291). CC {ECO:0000269|PubMed:2191291, ECO:0000269|PubMed:367445}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=40 uM for L-methionine {ECO:0000269|PubMed:4297674}; CC KM=20 uM for methionine {ECO:0000269|PubMed:7932711}; CC KM=300 uM for ATP {ECO:0000269|PubMed:4297674}; CC KM=410 uM for ATP {ECO:0000269|PubMed:7932711}; CC Note=kcat is 55 sec(-1). {ECO:0000269|PubMed:7932711}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:367445, CC ECO:0000269|PubMed:4605346}. CC -!- INTERACTION: CC P00959; P60422: rplB; NbExp=2; IntAct=EBI-909268, EBI-543515; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. CC -!- INDUCTION: Can be transcribed in vivo and in vitro from two distinct CC promoters separated by 510 nucleotides (PubMed:2259334). Methionine CC starvation has no effect on metG expression (PubMed:2259334). CC Repression is observed in a methionyl-tRNA synthetase overproducing CC strain (PubMed:2259334). {ECO:0000269|PubMed:2259334}. CC -!- DOMAIN: Binding of methionine promotes conformational changes within CC the active site. {ECO:0000269|PubMed:12946347}. CC -!- DISRUPTION PHENOTYPE: The mutant is defective in the synthesis of CC homocysteine thiolactone. {ECO:0000269|PubMed:2191291}. CC -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family. CC MetG type 1 subfamily. {ECO:0000255|HAMAP-Rule:MF_00098, ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA60526.1; Type=Erroneous initiation; Evidence={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; K02671; AAA24161.1; -; Genomic_DNA. DR EMBL; X55791; CAA39315.1; -; Genomic_DNA. DR EMBL; U00007; AAA60526.1; ALT_INIT; Genomic_DNA. DR EMBL; U00096; AAC75175.1; -; Genomic_DNA. DR EMBL; AP009048; BAE76592.1; -; Genomic_DNA. DR PIR; S14427; SYECMT. DR RefSeq; NP_416617.1; NC_000913.3. DR RefSeq; WP_001350533.1; NZ_CP009789.1. DR PDB; 1F4L; X-ray; 1.85 A; A=1-551. DR PDB; 1MEA; NMR; -; A=139-164. DR PDB; 1MED; NMR; -; A=139-164. DR PDB; 1P7P; X-ray; 1.80 A; A=2-552. DR PDB; 1PFU; X-ray; 1.91 A; A=2-552. DR PDB; 1PFV; X-ray; 1.70 A; A=2-552. DR PDB; 1PFW; X-ray; 1.78 A; A=2-552. DR PDB; 1PFY; X-ray; 1.93 A; A=2-552. DR PDB; 1PG0; X-ray; 1.90 A; A=2-552. DR PDB; 1PG2; X-ray; 1.75 A; A=2-552. DR PDB; 1QQT; X-ray; 2.03 A; A=2-552. DR PDB; 3H97; X-ray; 1.70 A; A=1-548. DR PDB; 3H99; X-ray; 1.40 A; A=1-548. DR PDB; 3H9B; X-ray; 1.50 A; A=1-548. DR PDB; 3H9C; X-ray; 1.40 A; A=2-548. DR PDB; 6SPN; X-ray; 1.45 A; A=2-548. DR PDB; 6SPO; X-ray; 1.20 A; A=2-548. DR PDB; 6SPP; X-ray; 1.49 A; A=2-548. DR PDB; 6SPQ; X-ray; 1.38 A; A=2-548. DR PDB; 6SPR; X-ray; 1.48 A; A=2-548. DR PDB; 8BRU; X-ray; 1.55 A; A=2-548. DR PDB; 8BRV; X-ray; 1.53 A; A=2-548. DR PDB; 8BRW; X-ray; 1.73 A; A=2-548. DR PDB; 8BRX; X-ray; 1.54 A; A=2-548. DR AlphaFoldDB; P00959; -. DR MDposit; P00959; -. DR MDRepo; P00959; -. DR SMR; P00959; -. DR BioGRID; 4259174; 19. DR BioGRID; 850988; 2. DR DIP; DIP-10194N; -. DR FunCoup; P00959; 892. DR IntAct; P00959; 4. DR STRING; 511145.b2114; -. DR BindingDB; P00959; -. DR ChEMBL; CHEMBL3367; -. DR DrugBank; DB02229; 5'-O-[(L-methionyl)-sulphamoyl]adenosine. DR DrugBank; DB03816; Difluoromethionine. DR DrugBank; DB04015; Methionine Phosphinate. DR DrugBank; DB02151; Methionine Phosphonate. DR DrugBank; DB03799; Trifluoromethionine. DR jPOST; P00959; -. DR PaxDb; 511145-b2114; -. DR EnsemblBacteria; AAC75175; AAC75175; b2114. DR GeneID; 946643; -. DR KEGG; ecj:JW2101; -. DR KEGG; eco:b2114; -. DR KEGG; ecoc:C3026_11860; -. DR PATRIC; fig|1411691.4.peg.133; -. DR EchoBASE; EB0581; -. DR eggNOG; COG0073; Bacteria. DR eggNOG; COG0143; Bacteria. DR HOGENOM; CLU_009710_7_0_6; -. DR InParanoid; P00959; -. DR OMA; NMFLPDR; -. DR OrthoDB; 9810191at2; -. DR PhylomeDB; P00959; -. DR BioCyc; EcoCyc:METG-MONOMER; -. DR BioCyc; MetaCyc:METG-MONOMER; -. DR BRENDA; 6.1.1.10; 2026. DR EvolutionaryTrace; P00959; -. DR PRO; PR:P00959; -. DR Proteomes; UP000000625; Chromosome. DR AbasyAtlas; P00959; -. DR GO; GO:0005829; C:cytosol; HDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule. DR GO; GO:0004825; F:methionine-tRNA ligase activity; IDA:EcoCyc. DR GO; GO:0042803; F:protein homodimerization activity; IDA:EcoCyc. DR GO; GO:0000049; F:tRNA binding; IEA:InterPro. DR GO; GO:0008270; F:zinc ion binding; IDA:EcoCyc. DR GO; GO:0071236; P:cellular response to antibiotic; IMP:EcoCyc. DR GO; GO:0006431; P:methionyl-tRNA aminoacylation; IMP:EcoCyc. DR CDD; cd07957; Anticodon_Ia_Met; 1. DR CDD; cd00814; MetRS_core; 1. DR CDD; cd02800; tRNA_bind_EcMetRS_like; 1. DR FunFam; 1.10.730.10:FF:000005; Methionine--tRNA ligase; 1. DR FunFam; 2.20.28.20:FF:000001; Methionine--tRNA ligase; 1. DR FunFam; 2.40.50.140:FF:000042; Methionine--tRNA ligase; 1. DR Gene3D; 3.40.50.620; HUPs; 1. DR Gene3D; 1.10.730.10; Isoleucyl-tRNA Synthetase, Domain 1; 1. DR Gene3D; 2.20.28.20; Methionyl-tRNA synthetase, Zn-domain; 1. DR Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 1. DR HAMAP; MF_00098; Met_tRNA_synth_type1; 1. DR InterPro; IPR001412; aa-tRNA-synth_I_CS. DR InterPro; IPR041872; Anticodon_Met. DR InterPro; IPR004495; Met-tRNA-synth_bsu_C. DR InterPro; IPR023458; Met-tRNA_ligase_1. DR InterPro; IPR014758; Met-tRNA_synth. DR InterPro; IPR015413; Methionyl/Leucyl_tRNA_Synth. DR InterPro; IPR033911; MetRS_core. DR InterPro; IPR029038; MetRS_Zn. DR InterPro; IPR012340; NA-bd_OB-fold. DR InterPro; IPR014729; Rossmann-like_a/b/a_fold. DR InterPro; IPR002547; tRNA-bd_dom. DR InterPro; IPR009080; tRNAsynth_Ia_anticodon-bd. DR NCBIfam; TIGR00398; metG; 1. DR NCBIfam; TIGR00399; metG_C_term; 1. DR NCBIfam; NF001100; PRK00133.1; 1. DR PANTHER; PTHR45765; METHIONINE--TRNA LIGASE; 1. DR PANTHER; PTHR45765:SF1; METHIONINE--TRNA LIGASE, CYTOPLASMIC; 1. DR Pfam; PF19303; Anticodon_3; 1. DR Pfam; PF09334; tRNA-synt_1g; 1. DR Pfam; PF01588; tRNA_bind; 1. DR PRINTS; PR01041; TRNASYNTHMET. DR SUPFAM; SSF47323; Anticodon-binding domain of a subclass of class I aminoacyl-tRNA synthetases; 1. DR SUPFAM; SSF57770; Methionyl-tRNA synthetase (MetRS), Zn-domain; 1. DR SUPFAM; SSF50249; Nucleic acid-binding proteins; 1. DR SUPFAM; SSF52374; Nucleotidylyl transferase; 1. DR PROSITE; PS00178; AA_TRNA_LIGASE_I; 1. DR PROSITE; PS50886; TRBD; 1. DR PDBsum; 1F4L; -. DR PDBsum; 1MEA; -. DR PDBsum; 1MED; -. DR PDBsum; 1P7P; -. DR PDBsum; 1PFU; -. DR PDBsum; 1PFV; -. DR PDBsum; 1PFW; -. DR PDBsum; 1PFY; -. DR PDBsum; 1PG0; -. DR PDBsum; 1PG2; -. DR PDBsum; 1QQT; -. DR PDBsum; 3H97; -. DR PDBsum; 3H99; -. DR PDBsum; 3H9B; -. DR PDBsum; 3H9C; -. DR PDBsum; 6SPN; -. DR PDBsum; 6SPO; -. DR PDBsum; 6SPP; -. DR PDBsum; 6SPQ; -. DR PDBsum; 6SPR; -. DR PDBsum; 8BRU; -. DR PDBsum; 8BRV; -. DR PDBsum; 8BRW; -. DR PDBsum; 8BRX; -. PE 1: Evidence at protein level; KW 3D-structure; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm; KW Direct protein sequencing; Ligase; Metal-binding; Nucleotide-binding; KW Protein biosynthesis; Reference proteome; RNA-binding; tRNA-binding; Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:4605346" FT CHAIN 2..677 FT /note="Methionine--tRNA ligase" FT /id="PRO_0000139129" FT DOMAIN 575..677 FT /note="tRNA-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00209" FT MOTIF 15..25 FT /note="'HIGH' region" FT /evidence="ECO:0000305" FT MOTIF 333..337 FT /note="'KMSKS' region" FT /evidence="ECO:0000305|PubMed:7932711" FT BINDING 14 FT /ligand="L-methionine" FT /ligand_id="ChEBI:CHEBI:57844" FT /evidence="ECO:0000269|PubMed:11243794, FT ECO:0000269|PubMed:12946347, ECO:0007744|PDB:1F4L, FT ECO:0007744|PDB:1PG2" FT BINDING 53 FT /ligand="L-methionine" FT /ligand_id="ChEBI:CHEBI:57844" FT /evidence="ECO:0000269|PubMed:11243794, FT ECO:0000269|PubMed:12946347, ECO:0007744|PDB:1F4L, FT ECO:0007744|PDB:1PG2" FT BINDING 146 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:10600385, FT ECO:0000269|PubMed:11243794, ECO:0000269|PubMed:12946347, FT ECO:0000269|PubMed:8515465, ECO:0000269|PubMed:8515466, FT ECO:0007744|PDB:1F4L, ECO:0007744|PDB:1MEA, FT ECO:0007744|PDB:1MED, ECO:0007744|PDB:1P7P, FT ECO:0007744|PDB:1PFU, ECO:0007744|PDB:1PFV, FT ECO:0007744|PDB:1PFW, ECO:0007744|PDB:1PFY, FT ECO:0007744|PDB:1QQT" FT BINDING 149 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:10600385, FT ECO:0000269|PubMed:11243794, ECO:0000269|PubMed:12946347, FT ECO:0000269|PubMed:8515465, ECO:0000269|PubMed:8515466, FT ECO:0007744|PDB:1F4L, ECO:0007744|PDB:1MEA, FT ECO:0007744|PDB:1MED, ECO:0007744|PDB:1P7P, FT ECO:0007744|PDB:1PFU, ECO:0007744|PDB:1PFV, FT ECO:0007744|PDB:1PFW, ECO:0007744|PDB:1PFY, FT ECO:0007744|PDB:1QQT" FT BINDING 159 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:10600385, FT ECO:0000269|PubMed:11243794, ECO:0000269|PubMed:12946347, FT ECO:0000269|PubMed:8515465, ECO:0000269|PubMed:8515466, FT ECO:0007744|PDB:1F4L, ECO:0007744|PDB:1MEA, FT ECO:0007744|PDB:1MED, ECO:0007744|PDB:1P7P, FT ECO:0007744|PDB:1PFU, ECO:0007744|PDB:1PFV, FT ECO:0007744|PDB:1PFW, ECO:0007744|PDB:1PFY, FT ECO:0007744|PDB:1QQT" FT BINDING 162 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:10600385, FT ECO:0000269|PubMed:11243794, ECO:0000269|PubMed:12946347, FT ECO:0000269|PubMed:8515465, ECO:0000269|PubMed:8515466, FT ECO:0007744|PDB:1F4L, ECO:0007744|PDB:1MEA, FT ECO:0007744|PDB:1MED, ECO:0007744|PDB:1P7P, FT ECO:0007744|PDB:1PFU, ECO:0007744|PDB:1PFV, FT ECO:0007744|PDB:1PFW, ECO:0007744|PDB:1PFY, FT ECO:0007744|PDB:1QQT" FT BINDING 336 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:2254937" FT MUTAGEN 146 FT /note="C->A: Strong decrease in activity. Weakens zinc ion FT binding." FT /evidence="ECO:0000269|PubMed:8515465" FT MUTAGEN 149 FT /note="C->A: Strong decrease in activity. Weakens zinc ion FT binding." FT /evidence="ECO:0000269|PubMed:8515465" FT MUTAGEN 159 FT /note="C->A: Strong decrease in activity. Weakens zinc ion FT binding." FT /evidence="ECO:0000269|PubMed:8515465" FT MUTAGEN 162 FT /note="C->A: Strong decrease in activity. Weakens zinc ion FT binding." FT /evidence="ECO:0000269|PubMed:8515465" FT MUTAGEN 299 FT /note="V->A: 4-fold increase in KM for methionine." FT /evidence="ECO:0000269|PubMed:1959615" FT MUTAGEN 302 FT /note="H->A: Strong increase in KM for methionine." FT /evidence="ECO:0000269|PubMed:1959615" FT MUTAGEN 306 FT /note="W->A: Strong increase in KM for methionine, whereas FT the KM for ATP does not vary by more than 50%." FT /evidence="ECO:0000269|PubMed:1959615" FT MUTAGEN 306 FT /note="W->F: Small decrease in KM for methionine." FT /evidence="ECO:0000269|PubMed:1959615" FT MUTAGEN 331 FT /note="G->A: Decrease in catalytic efficiency." FT /evidence="ECO:0000269|PubMed:7932711" FT MUTAGEN 331 FT /note="G->P: Strong decrease in catalytic efficiency." FT /evidence="ECO:0000269|PubMed:7932711" FT MUTAGEN 333 FT /note="K->A,Q: Loss of activity." FT /evidence="ECO:0000269|PubMed:7932711" FT MUTAGEN 334..337 FT /note="MSKS->FGKT: Loss of activity." FT /evidence="ECO:0000269|PubMed:7932711" FT MUTAGEN 334 FT /note="M->A: Strong decrease in catalytic efficiency." FT /evidence="ECO:0000269|PubMed:7932711" FT MUTAGEN 335 FT /note="S->A: Strong decrease in catalytic efficiency." FT /evidence="ECO:0000269|PubMed:7932711" FT MUTAGEN 337 FT /note="S->A: Strong decrease in catalytic efficiency." FT /evidence="ECO:0000269|PubMed:7932711" FT MUTAGEN 338 FT /note="R->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:7932711" FT MUTAGEN 338 FT /note="R->K: Decrease in catalytic efficiency." FT /evidence="ECO:0000269|PubMed:7932711" FT MUTAGEN 339 FT /note="G->A: Small increase in catalytic efficiency." FT /evidence="ECO:0000269|PubMed:7932711" FT MUTAGEN 339 FT /note="G->P: Decrease in catalytic efficiency." FT /evidence="ECO:0000269|PubMed:7932711" FT CONFLICT 2 FT /note="T -> A (in Ref. 7; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 6 FT /note="K -> E (in Ref. 7; AA sequence)" FT /evidence="ECO:0000305" FT STRAND 7..12 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 13..15 FT /evidence="ECO:0007829|PDB:6SPO" FT STRAND 16..19 FT /evidence="ECO:0007829|PDB:1QQT" FT HELIX 23..41 FT /evidence="ECO:0007829|PDB:6SPO" FT STRAND 45..53 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 57..66 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 70..87 FT /evidence="ECO:0007829|PDB:6SPO" FT STRAND 93..100 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 101..116 FT /evidence="ECO:0007829|PDB:6SPO" FT STRAND 120..130 FT /evidence="ECO:0007829|PDB:6SPO" FT TURN 131..134 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 139..141 FT /evidence="ECO:0007829|PDB:6SPO" FT STRAND 142..145 FT /evidence="ECO:0007829|PDB:6SPO" FT TURN 147..149 FT /evidence="ECO:0007829|PDB:6SPO" FT STRAND 152..155 FT /evidence="ECO:0007829|PDB:6SPO" FT TURN 160..162 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 168..170 FT /evidence="ECO:0007829|PDB:6SPO" FT STRAND 172..176 FT /evidence="ECO:0007829|PDB:6SPO" FT TURN 177..179 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 181..183 FT /evidence="ECO:0007829|PDB:6SPO" FT STRAND 184..193 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 195..198 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 199..206 FT /evidence="ECO:0007829|PDB:6SPO" FT TURN 207..209 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 213..225 FT /evidence="ECO:0007829|PDB:6SPO" FT STRAND 233..237 FT /evidence="ECO:0007829|PDB:6SPO" FT STRAND 249..251 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 253..272 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 277..282 FT /evidence="ECO:0007829|PDB:6SPO" FT STRAND 288..295 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 296..298 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 301..305 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 306..312 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 316..318 FT /evidence="ECO:0007829|PDB:6SPO" FT STRAND 319..324 FT /evidence="ECO:0007829|PDB:6SPO" FT STRAND 327..329 FT /evidence="ECO:0007829|PDB:6SPO" FT TURN 336..339 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 344..350 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 353..363 FT /evidence="ECO:0007829|PDB:6SPO" FT STRAND 371..373 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 375..381 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 382..391 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 392..395 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 398..404 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 416..424 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 426..434 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 438..459 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 461..464 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 471..492 FT /evidence="ECO:0007829|PDB:6SPO" FT TURN 493..495 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 497..507 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 514..517 FT /evidence="ECO:0007829|PDB:6SPO" FT HELIX 525..527 FT /evidence="ECO:0007829|PDB:1PG0" FT HELIX 537..547 FT /evidence="ECO:0007829|PDB:6SPO" SQ SEQUENCE 677 AA; 76255 MW; 363F3324AFD3202C CRC64; MTQVAKKILV TCALPYANGS IHLGHMLEHI QADVWVRYQR MRGHEVNFIC ADDAHGTPIM LKAQQLGITP EQMIGEMSQE HQTDFAGFNI SYDNYHSTHS EENRQLSELI YSRLKENGFI KNRTISQLYD PEKGMFLPDR FVKGTCPKCK SPDQYGDNCE VCGATYSPTE LIEPKSVVSG ATPVMRDSEH FFFDLPSFSE MLQAWTRSGA LQEQVANKMQ EWFESGLQQW DISRDAPYFG FEIPNAPGKY FYVWLDAPIG YMGSFKNLCD KRGDSVSFDE YWKKDSTAEL YHFIGKDIVY FHSLFWPAML EGSNFRKPSN LFVHGYVTVN GAKMSKSRGT FIKASTWLNH FDADSLRYYY TAKLSSRIDD IDLNLEDFVQ RVNADIVNKV VNLASRNAGF INKRFDGVLA SELADPQLYK TFTDAAEVIG EAWESREFGK AVREIMALAD LANRYVDEQA PWVVAKQEGR DADLQAICSM GINLFRVLMT YLKPVLPKLT ERAEAFLNTE LTWDGIQQPL LGHKVNPFKA LYNRIDMRQV EALVEASKEE VKAAAAPVTG PLADDPIQET ITFDDFAKVD LRVALIENAE FVEGSDKLLR LTLDLGGEKR NVFSGIRSAY PDPQALIGRH TIMVANLAPR KMRFGISEGM VMAAGPGGKD IFLLSPDAGA KPGHQVK //