ID   METB_ECOLI              Reviewed;         386 AA.
AC   P00935; Q2M8N5;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   02-SEP-2026, entry version 203.
DE   RecName: Full=Cystathionine gamma-synthase;
DE            Short=CGS;
DE            EC=2.5.1.48;
DE   AltName: Full=O-succinylhomoserine (thiol)-lyase;
GN   Name=metB; OrderedLocusNames=b3939, JW3910;
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].
RC   STRAIN=K12;
RX   PubMed=6361020; DOI=10.1016/s0021-9258(17)43743-4;
RA   Duchange N., Zakin M.M., Ferrara P., Saint-Girons I., Park I., Tran S.V.,
RA   Py M.-C., Cohen G.N.;
RT   "Structure of the metJBLF cluster in Escherichia coli K12. Sequence of the
RT   metB structural gene and of the 5'- and 3'-flanking regions of the metBL
RT   operon.";
RL   J. Biol. Chem. 258:14868-14871(1983).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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   [3]
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   [4]
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   [5]
RP   PROTEIN SEQUENCE OF 182-209.
RX   PubMed=3307782; DOI=10.1016/0006-291x(87)90968-5;
RA   Martel A., Bouthier de la Tour C., Le Goffic F.;
RT   "Pyridoxal 5'phosphate binding site of Escherichia coli beta cystathionase
RT   and cystathionine gamma synthase comparison of their sequences.";
RL   Biochem. Biophys. Res. Commun. 147:565-571(1987).
RN   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP   SUBUNIT.
RX   PubMed=2405903; DOI=10.1021/bi00454a019;
RA   Holbrook E.L., Greene R.C., Krueger J.H.;
RT   "Purification and properties of cystathionine gamma-synthase from
RT   overproducing strains of Escherichia coli.";
RL   Biochemistry 29:435-442(1990).
RN   [7]
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   [8]
RP   X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS), SUBUNIT, AND PYRIDOXAL PHOSPHATE AT
RP   LYS-198.
RX   PubMed=9843488; DOI=10.1093/emboj/17.23.6827;
RA   Clausen T., Huber R., Prade L., Wahl M.C., Messerschmidt A.;
RT   "Crystal structure of Escherichia coli cystathionine gamma-synthase at 1.5-
RT   A resolution.";
RL   EMBO J. 17:6827-6838(1998).
CC   -!- FUNCTION: Catalyzes the formation of L-cystathionine from O-succinyl-L-
CC       homoserine (OSHS) and L-cysteine, via a gamma-replacement reaction. In
CC       the absence of thiol, catalyzes gamma-elimination to form 2-
CC       oxobutanoate, succinate and ammonia. {ECO:0000269|PubMed:2405903}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=O-succinyl-L-homoserine + L-cysteine = L,L-cystathionine +
CC         succinate + H(+); Xref=Rhea:RHEA:20397, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:30031, ChEBI:CHEBI:35235, ChEBI:CHEBI:57661,
CC         ChEBI:CHEBI:58161; EC=2.5.1.48;
CC         Evidence={ECO:0000269|PubMed:2405903};
CC   -!- COFACTOR:
CC       Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC         Evidence={ECO:0000269|PubMed:2405903};
CC       Note=Binds 1 pyridoxal phosphate per subunit.
CC       {ECO:0000269|PubMed:2405903};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.33 mM for O-succinyl-L-homoserine (at pH 8.2 and 25 degrees
CC         Celsius, when assaying the gamma-elimination reaction)
CC         {ECO:0000269|PubMed:2405903};
CC         KM=1 mM for O-succinyl-L-homoserine (at pH 8.2 and 25 degrees
CC         Celsius, when assaying the gamma-replacement reaction)
CC         {ECO:0000269|PubMed:2405903};
CC         KM=0.05 mM for L-cysteine (at pH 8.2 and 25 degrees Celsius, when
CC         assaying the gamma-replacement reaction)
CC         {ECO:0000269|PubMed:2405903};
CC         Note=kcat are 700 min(-1) and 460 min(-1) for the gamma-replacement
CC         and gamma-elimination reaction, respectively.;
CC       pH dependence:
CC         Optimum pH is 7.8 for the gamma-replacement reaction.
CC         {ECO:0000269|PubMed:2405903};
CC   -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC       pathway; L-cystathionine from O-succinyl-L-homoserine: step 1/1.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:2405903,
CC       ECO:0000269|PubMed:9843488}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- SIMILARITY: Belongs to the trans-sulfuration enzymes family.
CC       {ECO:0000305}.
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DR   EMBL; AH000886; AAA24167.1; -; Genomic_DNA.
DR   EMBL; L19201; AAB03071.1; -; Genomic_DNA.
DR   EMBL; U00096; AAC76921.1; -; Genomic_DNA.
DR   EMBL; AP009048; BAE77371.1; -; Genomic_DNA.
DR   PIR; A01158; SYECCG.
DR   RefSeq; NP_418374.1; NC_000913.3.
DR   RefSeq; WP_001295694.1; NZ_CP010442.1.
DR   PDB; 1CS1; X-ray; 1.50 A; A/B/C/D=1-386.
DR   AlphaFoldDB; P00935; -.
DR   SMR; P00935; -.
DR   BioGRID; 4261102; 20.
DR   BioGRID; 852731; 1.
DR   DIP; DIP-10192N; -.
DR   FunCoup; P00935; 779.
DR   IntAct; P00935; 1.
DR   STRING; 511145.b3939; -.
DR   DrugBank; DB04083; N(6)-(pyridoxal phosphate)-L-lysine.
DR   jPOST; P00935; -.
DR   PaxDb; 511145-b3939; -.
DR   EnsemblBacteria; AAC76921; AAC76921; b3939.
DR   GeneID; 948434; -.
DR   KEGG; ecj:JW3910; -.
DR   KEGG; eco:b3939; -.
DR   KEGG; ecoc:C3026_21285; -.
DR   PATRIC; fig|1411691.4.peg.2766; -.
DR   EchoBASE; EB0577; -.
DR   eggNOG; COG0626; Bacteria.
DR   HOGENOM; CLU_018986_2_0_6; -.
DR   InParanoid; P00935; -.
DR   OMA; NCIGATG; -.
DR   OrthoDB; 9805807at2; -.
DR   PhylomeDB; P00935; -.
DR   BioCyc; EcoCyc:O-SUCCHOMOSERLYASE-MONOMER; -.
DR   BioCyc; MetaCyc:O-SUCCHOMOSERLYASE-MONOMER; -.
DR   BRENDA; 2.5.1.48; 2026.
DR   SABIO-RK; P00935; -.
DR   UniPathway; UPA00051; UER00077.
DR   EvolutionaryTrace; P00935; -.
DR   PRO; PR:P00935; -.
DR   Proteomes; UP000000625; Chromosome.
DR   AbasyAtlas; P00935; -.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0004123; F:cystathionine gamma-lyase activity; IBA:GO_Central.
DR   GO; GO:0003962; F:cystathionine gamma-synthase activity; IDA:EcoCyc.
DR   GO; GO:0030170; F:pyridoxal phosphate binding; IDA:EcoCyc.
DR   GO; GO:0019346; P:transsulfuration; IBA:GO_Central.
DR   CDD; cd00614; CGS_like; 1.
DR   FunFam; 3.40.640.10:FF:000038; Cystathionine gamma-synthase; 1.
DR   FunFam; 3.90.1150.10:FF:000008; Cystathionine gamma-synthase; 1.
DR   Gene3D; 3.90.1150.10; Aspartate Aminotransferase, domain 1; 1.
DR   Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 1.
DR   InterPro; IPR000277; Cys/Met-Metab_PyrdxlP-dep_enz.
DR   InterPro; IPR054542; Cys_met_metab_PP.
DR   InterPro; IPR011821; O_succ_thio_ly.
DR   InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR   InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR   InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR   NCBIfam; TIGR02080; O_succ_thio_ly; 1.
DR   NCBIfam; NF005961; PRK08045.1; 1.
DR   PANTHER; PTHR11808:SF75; CYSTATHIONINE GAMMA-SYNTHASE; 1.
DR   PANTHER; PTHR11808; TRANS-SULFURATION ENZYME FAMILY MEMBER; 1.
DR   Pfam; PF01053; Cys_Met_Meta_PP; 1.
DR   PIRSF; PIRSF001434; CGS; 1.
DR   SUPFAM; SSF53383; PLP-dependent transferases; 1.
DR   PROSITE; PS00868; CYS_MET_METAB_PP; 1.
DR   PDBsum; 1CS1; -.
PE   1: Evidence at protein level;
KW   3D-structure; Amino-acid biosynthesis; Cytoplasm;
KW   Direct protein sequencing; Methionine biosynthesis; Pyridoxal phosphate;
KW   Reference proteome; Transferase.
FT   CHAIN           1..386
FT                   /note="Cystathionine gamma-synthase"
FT                   /id="PRO_0000114756"
FT   MOD_RES         198
FT                   /note="N6-(pyridoxal phosphate)lysine"
FT                   /evidence="ECO:0000269|PubMed:3307782"
FT   HELIX           5..11
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   TURN            12..15
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   TURN            18..20
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   STRAND          22..24
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   STRAND          31..33
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   TURN            47..49
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   HELIX           52..65
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   STRAND          68..75
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   HELIX           76..87
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   STRAND          93..97
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   HELIX           102..112
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   TURN            113..115
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   STRAND          118..122
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   HELIX           127..135
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   STRAND          139..144
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   TURN            148..150
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   HELIX           156..165
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   STRAND          169..173
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   TURN            175..177
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   TURN            179..181
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   HELIX           184..187
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   STRAND          190..195
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   TURN            196..201
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   STRAND          209..215
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   HELIX           216..229
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   HELIX           235..245
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   HELIX           248..266
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   STRAND          272..276
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   HELIX           286..292
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   STRAND          298..306
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   HELIX           308..316
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   STRAND          319..325
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   STRAND          329..331
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   STRAND          333..336
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   HELIX           337..339
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   TURN            340..344
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   HELIX           347..353
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   STRAND          359..363
FT                   /evidence="ECO:0007829|PDB:1CS1"
FT   HELIX           369..383
FT                   /evidence="ECO:0007829|PDB:1CS1"
SQ   SEQUENCE   386 AA;  41550 MW;  423B825219A42E9E CRC64;
     MTRKQATIAV RSGLNDDEQY GCVVPPIHLS STYNFTGFNE PRAHDYSRRG NPTRDVVQRA
     LAELEGGAGA VLTNTGMSAI HLVTTVFLKP GDLLVAPHDC YGGSYRLFDS LAKRGCYRVL
     FVDQGDEQAL RAALAEKPKL VLVESPSNPL LRVVDIAKIC HLAREVGAVS VVDNTFLSPA
     LQNPLALGAD LVLHSCTKYL NGHSDVVAGV VIAKDPDVVT ELAWWANNIG VTGGAFDSYL
     LLRGLRTLVP RMELAQRNAQ AIVKYLQTQP LVKKLYHPSL PENQGHEIAA RQQKGFGAML
     SFELDGDEQT LRRFLGGLSL FTLAESLGGV ESLISHAATM THAGMAPEAR AAAGISETLL
     RISTGIEDGE DLIADLENGF RAANKG
//