METAS_ECOLI
ID METAS_ECOLI Reviewed; 309 AA.
AC P07623; Q2M6U1;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Homoserine O-succinyltransferase {ECO:0000255|HAMAP-Rule:MF_00295, ECO:0000303|PubMed:17442255};
DE Short=HST {ECO:0000255|HAMAP-Rule:MF_00295, ECO:0000303|PubMed:17442255};
DE EC=2.3.1.46 {ECO:0000269|PubMed:10572016, ECO:0000269|PubMed:17302437, ECO:0000269|PubMed:17442255, ECO:0000269|PubMed:28581482};
DE AltName: Full=Homoserine transsuccinylase {ECO:0000255|HAMAP-Rule:MF_00295, ECO:0000303|PubMed:10572016};
DE Short=HTS {ECO:0000255|HAMAP-Rule:MF_00295, ECO:0000303|PubMed:10572016};
GN Name=metAS {ECO:0000255|HAMAP-Rule:MF_00295, ECO:0000303|PubMed:28581482};
GN Synonyms=metA {ECO:0000303|PubMed:6094503};
GN OrderedLocusNames=b4013, JW3973;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=2654885; DOI=10.1093/nar/17.7.2856;
RA Cozzone A.J.;
RT "Nucleotide sequence of the metA gene encoding homoserine trans-succinylase
RT in Escherichia coli.";
RL Nucleic Acids Res. 17:2856-2856(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-21, FUNCTION,
RP CATALYTIC ACTIVITY, REACTION MECHANISM, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, SUBUNIT, AND ACTIVE SITE.
RX PubMed=10572016; DOI=10.1021/bi991710o;
RA Born T.L., Blanchard J.S.;
RT "Enzyme-catalyzed acylation of homoserine: mechanistic characterization of
RT the Escherichia coli metA-encoded homoserine transsuccinylase.";
RL Biochemistry 38:14416-14423(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=8265357; DOI=10.1093/nar/21.23.5408;
RA Blattner F.R., Burland V.D., Plunkett G. III, Sofia H.J., Daniels D.L.;
RT "Analysis of the Escherichia coli genome. IV. DNA sequence of the region
RT from 89.2 to 92.8 minutes.";
RL Nucleic Acids Res. 21:5408-5417(1993).
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 1-70, AND INDUCTION.
RC STRAIN=K12;
RX PubMed=6094503; DOI=10.1128/jb.160.3.1158-1162.1984;
RA Michaeli S., Mevarech M., Ron E.Z.;
RT "Regulatory region of the metA gene of Escherichia coli K-12.";
RL J. Bacteriol. 160:1158-1162(1984).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 207-309.
RC STRAIN=K12;
RX PubMed=3050899; DOI=10.1093/nar/16.19.9342;
RA Byrne C.R., Stokes H.W., Ward K.A.;
RT "Nucleotide sequence of the aceB gene encoding malate synthase A in
RT Escherichia coli.";
RL Nucleic Acids Res. 16:9342-9342(1988).
RN [8]
RP MUTAGENESIS OF 46-LYS-LYS-47.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=15556615; DOI=10.1016/j.febslet.2004.10.037;
RA Rosen R., Becher D., Buettner K., Biran D., Hecker M., Ron E.Z.;
RT "Probing the active site of homoserine trans-succinylase.";
RL FEBS Lett. 577:386-392(2004).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM, BIOPHYSICOCHEMICAL
RP PROPERTIES, MUTAGENESIS OF LYS-46; LYS-47; CYS-142; LYS-157; ARG-193;
RP HIS-235; GLU-237; TYR-238; GLU-246 AND ARG-249, AND ACTIVE SITE.
RX PubMed=17442255; DOI=10.1016/j.abb.2007.03.004;
RA Coe D.M., Viola R.E.;
RT "Assessing the roles of essential functional groups in the mechanism of
RT homoserine succinyltransferase.";
RL Arch. Biochem. Biophys. 461:211-218(2007).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM, BIOPHYSICOCHEMICAL
RP PROPERTIES, MUTAGENESIS OF LYS-46; LYS-47; CYS-90; CYS-142 AND HIS-235, AND
RP ACTIVE SITE.
RX PubMed=17302437; DOI=10.1021/bi0620252;
RA Ziegler K., Noble S.M., Mutumanje E., Bishop B., Huddler D.P., Born T.L.;
RT "Identification of catalytic cysteine, histidine, and lysine residues in
RT Escherichia coli homoserine transsuccinylase.";
RL Biochemistry 46:2674-2683(2007).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=28581482; DOI=10.1038/nchembio.2397;
RA Bastard K., Perret A., Mariage A., Bessonnet T., Pinet-Turpault A.,
RA Petit J.L., Darii E., Bazire P., Vergne-Vaxelaire C., Brewee C., Debard A.,
RA Pellouin V., Besnard-Gonnet M., Artiguenave F., Medigue C., Vallenet D.,
RA Danchin A., Zaparucha A., Weissenbach J., Salanoubat M., de Berardinis V.;
RT "Parallel evolution of non-homologous isofunctional enzymes in methionine
RT biosynthesis.";
RL Nat. Chem. Biol. 13:858-866(2017).
CC -!- FUNCTION: Transfers a succinyl group from succinyl-CoA to L-homoserine,
CC forming succinyl-L-homoserine (PubMed:10572016, PubMed:17442255,
CC PubMed:17302437, PubMed:28581482). Utilizes a ping-pong kinetic
CC mechanism in which the succinyl group of succinyl-CoA is initially
CC transferred to the enzyme to form a succinyl-enzyme intermediate before
CC subsequent transfer to homoserine to form the final product, O-
CC succinylhomoserine (PubMed:10572016, PubMed:17442255, PubMed:17302437).
CC Cannot use acetyl-CoA (PubMed:10572016). {ECO:0000269|PubMed:10572016,
CC ECO:0000269|PubMed:17302437, ECO:0000269|PubMed:17442255,
CC ECO:0000269|PubMed:28581482}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-homoserine + succinyl-CoA = CoA + O-succinyl-L-homoserine;
CC Xref=Rhea:RHEA:22008, ChEBI:CHEBI:57287, ChEBI:CHEBI:57292,
CC ChEBI:CHEBI:57476, ChEBI:CHEBI:57661; EC=2.3.1.46;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00295,
CC ECO:0000269|PubMed:10572016, ECO:0000269|PubMed:17302437,
CC ECO:0000269|PubMed:17442255, ECO:0000269|PubMed:28581482};
CC -!- ACTIVITY REGULATION: Inhibited by iodoacetamide in a pH-dependent
CC manner. {ECO:0000269|PubMed:10572016}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.17 mM for succinyl-CoA {ECO:0000269|PubMed:10572016};
CC KM=0.13 mM for succinyl-CoA {ECO:0000269|PubMed:17302437};
CC KM=0.28 mM for succinyl-CoA {ECO:0000269|PubMed:17442255};
CC KM=1.6 mM for L-homoserine {ECO:0000269|PubMed:10572016};
CC KM=0.72 mM for L-homoserine {ECO:0000269|PubMed:17302437};
CC KM=0.38 mM for L-homoserine {ECO:0000269|PubMed:17442255};
CC KM=0.64 mM for CoA {ECO:0000269|PubMed:10572016};
CC KM=3.5 mM for O-succinylhomoserine {ECO:0000269|PubMed:10572016};
CC Note=kcat is 24 sec(-1) with succinyl-CoA as substrate. kcat is 24
CC sec(-1) with L-homoserine as substrate. kcat is 5.23 sec(-1) with CoA
CC as substrate. kcat is 5.23 sec(-1) with O-succinylhomoserine as
CC substrate. {ECO:0000269|PubMed:10572016};
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC pathway; O-succinyl-L-homoserine from L-homoserine: step 1/1.
CC {ECO:0000255|HAMAP-Rule:MF_00295, ECO:0000305|PubMed:10572016}.
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_00295,
CC ECO:0000269|PubMed:10572016}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00295,
CC ECO:0000305}.
CC -!- INDUCTION: Contains two transcription starting points, P1 and P2, which
CC are 74 bp apart. P1 is under negative control by methionine, whereas P2
CC is independent of the intracellular methionine concentration.
CC {ECO:0000269|PubMed:6094503}.
CC -!- SIMILARITY: Belongs to the MetA family. {ECO:0000255|HAMAP-
CC Rule:MF_00295, ECO:0000305}.
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DR EMBL; X14501; CAA32654.1; -; Genomic_DNA.
DR EMBL; U00006; AAC43107.1; -; Genomic_DNA.
DR EMBL; U00096; AAC76983.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE78015.1; -; Genomic_DNA.
DR EMBL; M10210; AAA24157.1; -; Genomic_DNA.
DR EMBL; X12431; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; D65208; XYECM.
DR RefSeq; NP_418437.1; NC_000913.3.
DR RefSeq; WP_001122779.1; NZ_LN832404.1.
DR PDB; 6MTG; X-ray; 1.85 A; A/B=1-296.
DR PDB; 7CBE; X-ray; 1.70 A; A/B=1-309.
DR PDBsum; 6MTG; -.
DR PDBsum; 7CBE; -.
DR AlphaFoldDB; P07623; -.
DR SMR; P07623; -.
DR BioGRID; 4259289; 20.
DR IntAct; P07623; 2.
DR MINT; P07623; -.
DR STRING; 511145.b4013; -.
DR PaxDb; P07623; -.
DR PRIDE; P07623; -.
DR EnsemblBacteria; AAC76983; AAC76983; b4013.
DR EnsemblBacteria; BAE78015; BAE78015; BAE78015.
DR GeneID; 948513; -.
DR KEGG; ecj:JW3973; -.
DR KEGG; eco:b4013; -.
DR PATRIC; fig|1411691.4.peg.2700; -.
DR EchoBASE; EB0576; -.
DR eggNOG; COG1897; Bacteria.
DR HOGENOM; CLU_057851_0_1_6; -.
DR InParanoid; P07623; -.
DR OMA; WLWFCYQ; -.
DR PhylomeDB; P07623; -.
DR BioCyc; EcoCyc:HOMSUCTRAN-MON; -.
DR BioCyc; MetaCyc:HOMSUCTRAN-MON; -.
DR BRENDA; 2.3.1.46; 2026.
DR SABIO-RK; P07623; -.
DR UniPathway; UPA00051; UER00075.
DR PRO; PR:P07623; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004414; F:homoserine O-acetyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008899; F:homoserine O-succinyltransferase activity; IDA:EcoCyc.
DR GO; GO:0019281; P:L-methionine biosynthetic process from homoserine via O-succinyl-L-homoserine and cystathionine; IEA:InterPro.
DR CDD; cd03131; GATase1_HTS; 1.
DR Gene3D; 3.40.50.880; -; 1.
DR HAMAP; MF_00295; MetA_acyltransf; 1.
DR InterPro; IPR029062; Class_I_gatase-like.
DR InterPro; IPR005697; HST_MetA.
DR InterPro; IPR033752; MetA_family.
DR PANTHER; PTHR20919; PTHR20919; 1.
DR Pfam; PF04204; HTS; 1.
DR PIRSF; PIRSF000450; H_ser_succinyltr; 1.
DR SUPFAM; SSF52317; SSF52317; 1.
DR TIGRFAMs; TIGR01001; metA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Amino-acid biosynthesis; Cytoplasm;
KW Direct protein sequencing; Methionine biosynthesis; Reference proteome;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:10572016"
FT CHAIN 2..309
FT /note="Homoserine O-succinyltransferase"
FT /id="PRO_0000199748"
FT ACT_SITE 142
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00295,
FT ECO:0000305|PubMed:10572016, ECO:0000305|PubMed:17302437,
FT ECO:0000305|PubMed:17442255"
FT ACT_SITE 235
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00295,
FT ECO:0000305|PubMed:17302437, ECO:0000305|PubMed:17442255"
FT ACT_SITE 237
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00295,
FT ECO:0000305|PubMed:17302437, ECO:0000305|PubMed:17442255"
FT BINDING 163
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00295"
FT BINDING 192
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00295"
FT BINDING 249
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00295"
FT SITE 111
FT /note="Important for acyl-CoA specificity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00295"
FT SITE 192
FT /note="Important for substrate specificity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00295"
FT MUTAGEN 46..47
FT /note="KK->AA: Lack of activity."
FT /evidence="ECO:0000269|PubMed:15556615,
FT ECO:0000269|PubMed:17302437, ECO:0000269|PubMed:17442255"
FT MUTAGEN 46
FT /note="K->A: 16-fold decrease in Km for L-homoserine. 32-
FT fold decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:17302437"
FT MUTAGEN 46
FT /note="K->L: 6-fold increase in Km for L-homoserine and in
FT Km for succinyl-CoA. Slight increase in catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:17442255"
FT MUTAGEN 46
FT /note="K->R: Slight decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:17302437"
FT MUTAGEN 47
FT /note="K->A: 22-fold decrease in Km for L-homoserine.
FT Almost loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:17302437"
FT MUTAGEN 47
FT /note="K->L: 8-fold decrease in Km for L-homoserine and 10-
FT fold increase in Km for succinyl-CoA. 20-fold decrease in
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:17442255"
FT MUTAGEN 47
FT /note="K->R: 14-fold decrease in Km for L-homoserine. 72-
FT fold decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:17302437"
FT MUTAGEN 90
FT /note="C->A,S: No change in activity."
FT /evidence="ECO:0000269|PubMed:17302437"
FT MUTAGEN 142
FT /note="C->A,S: Lack of activity."
FT /evidence="ECO:0000269|PubMed:17302437,
FT ECO:0000269|PubMed:17442255"
FT MUTAGEN 157
FT /note="K->L: Lack of activity."
FT /evidence="ECO:0000269|PubMed:17442255"
FT MUTAGEN 193
FT /note="R->A: 3-fold increase in Km for L-homoserine. 8-fold
FT decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:17442255"
FT MUTAGEN 193
FT /note="R->K: 8-fold decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:17442255"
FT MUTAGEN 235
FT /note="H->A,N: Lack of activity."
FT /evidence="ECO:0000269|PubMed:17302437,
FT ECO:0000269|PubMed:17442255"
FT MUTAGEN 237
FT /note="E->A: 32-fold decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:17442255"
FT MUTAGEN 237
FT /note="E->D: 3-fold decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:17442255"
FT MUTAGEN 238
FT /note="Y->F: 5-fold increase in Km for L-homoserine."
FT /evidence="ECO:0000269|PubMed:17442255"
FT MUTAGEN 246
FT /note="E->A: 150-fold increase in Km for L-homoserine."
FT /evidence="ECO:0000269|PubMed:17442255"
FT MUTAGEN 246
FT /note="E->D: 24-fold increase in Km for L-homoserine."
FT /evidence="ECO:0000269|PubMed:17442255"
FT MUTAGEN 249
FT /note="R->K: 4-fold increase in Km for L-homoserine."
FT /evidence="ECO:0000269|PubMed:17442255"
FT CONFLICT 67
FT /note="I -> V (in Ref. 1 and 6)"
FT /evidence="ECO:0000305"
FT STRAND 3..5
FT /evidence="ECO:0007829|PDB:7CBE"
FT HELIX 11..17
FT /evidence="ECO:0007829|PDB:7CBE"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:7CBE"
FT STRAND 36..41
FT /evidence="ECO:0007829|PDB:7CBE"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:6MTG"
FT HELIX 47..58
FT /evidence="ECO:0007829|PDB:7CBE"
FT STRAND 60..63
FT /evidence="ECO:0007829|PDB:7CBE"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:7CBE"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:6MTG"
FT HELIX 83..88
FT /evidence="ECO:0007829|PDB:7CBE"
FT HELIX 92..95
FT /evidence="ECO:0007829|PDB:7CBE"
FT STRAND 100..105
FT /evidence="ECO:0007829|PDB:7CBE"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:7CBE"
FT HELIX 121..134
FT /evidence="ECO:0007829|PDB:7CBE"
FT STRAND 135..141
FT /evidence="ECO:0007829|PDB:7CBE"
FT HELIX 143..153
FT /evidence="ECO:0007829|PDB:7CBE"
FT STRAND 159..173
FT /evidence="ECO:0007829|PDB:7CBE"
FT TURN 179..182
FT /evidence="ECO:0007829|PDB:7CBE"
FT STRAND 185..195
FT /evidence="ECO:0007829|PDB:7CBE"
FT HELIX 199..206
FT /evidence="ECO:0007829|PDB:7CBE"
FT STRAND 209..214
FT /evidence="ECO:0007829|PDB:7CBE"
FT STRAND 217..223
FT /evidence="ECO:0007829|PDB:7CBE"
FT STRAND 227..232
FT /evidence="ECO:0007829|PDB:7CBE"
FT HELIX 242..252
FT /evidence="ECO:0007829|PDB:7CBE"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:7CBE"
FT HELIX 278..291
FT /evidence="ECO:0007829|PDB:7CBE"
FT TURN 292..294
FT /evidence="ECO:0007829|PDB:7CBE"
SQ SEQUENCE 309 AA; 35727 MW; A2C395A9A9CFE2C0 CRC64;
MPIRVPDELP AVNFLREENV FVMTTSRASG QEIRPLKVLI LNLMPKKIET ENQFLRLLSN
SPLQVDIQLL RIDSRESRNT PAEHLNNFYC NFEDIQDQNF DGLIVTGAPL GLVEFNDVAY
WPQIKQVLEW SKDHVTSTLF VCWAVQAALN ILYGIPKQTR TEKLSGVYEH HILHPHALLT
RGFDDSFLAP HSRYADFPAA LIRDYTDLEI LAETEEGDAY LFASKDKRIA FVTGHPEYDA
QTLAQEFFRD VEAGLDPDVP YNYFPHNDPQ NTPRASWRSH GNLLFTNWLN YYVYQITPYD
LRHMNPTLD
