ID   EGTA_MYCTU              Reviewed;         432 AA.
AC   P9WPK7; L0TDK0; O69672; Q7D512;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   25-MAY-2022, entry version 46.
DE   RecName: Full=Glutamate--cysteine ligase EgtA;
DE            EC=6.3.2.2 {ECO:0000269|PubMed:16262797};
DE   AltName: Full=Gamma-glutamylcysteine synthase {ECO:0000303|PubMed:16262797};
DE            Short=GCS;
DE            Short=Gamma-ECS;
GN   Name=egtA; Synonyms=gshA {ECO:0000303|PubMed:16262797};
GN   OrderedLocusNames=Rv3704c;
OS   Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycobacterium; Mycobacterium tuberculosis complex.
OX   NCBI_TaxID=83332;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=9634230; DOI=10.1038/31159;
RA   Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA   Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA   Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA   Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA   Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA   Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA   Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA   Barrell B.G.;
RT   "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT   genome sequence.";
RL   Nature 393:537-544(1998).
RN   [2]
RP   PROTEIN SEQUENCE OF 1-10, FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY
RP   REGULATION.
RC   STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX   PubMed=16262797; DOI=10.1111/j.1365-2958.2005.04899.x;
RA   Harth G., Maslesa-Galic S., Tullius M.V., Horwitz M.A.;
RT   "All four Mycobacterium tuberculosis glnA genes encode glutamine synthetase
RT   activities but only GlnA1 is abundantly expressed and essential for
RT   bacterial homeostasis.";
RL   Mol. Microbiol. 58:1157-1172(2005).
RN   [3]
RP   IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX   PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA   Raman K., Yeturu K., Chandra N.;
RT   "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT   through an interactome, reactome and genome-scale structural analysis.";
RL   BMC Syst. Biol. 2:109-109(2008).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA   Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA   Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA   Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA   Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT   "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT   mass spectrometry.";
RL   Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC   -!- FUNCTION: Catalyzes the synthesis of gamma-glutamylcysteine (gamma-GC)
CC       (PubMed:16262797). This compound is used as substrate for the
CC       biosynthesis of the low-molecular thiol compound ergothioneine (By
CC       similarity). {ECO:0000250|UniProtKB:A0R5N1,
CC       ECO:0000269|PubMed:16262797}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-cysteine + L-glutamate = ADP + gamma-L-glutamyl-L-
CC         cysteine + H(+) + phosphate; Xref=Rhea:RHEA:13285, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, ChEBI:CHEBI:35235,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:58173, ChEBI:CHEBI:456216; EC=6.3.2.2;
CC         Evidence={ECO:0000269|PubMed:16262797};
CC   -!- ACTIVITY REGULATION: Weakly inhibited by L-methionine-S,R-sulphoximine
CC       (MSO) and strongly inhibited by D,L-buthionine-S,R-sulphoximine (BSO)
CC       in vitro. {ECO:0000269|PubMed:16262797}.
CC   -!- PATHWAY: Amino-acid biosynthesis; ergothioneine biosynthesis.
CC       {ECO:0000250|UniProtKB:A0R5N1}.
CC   -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC       {ECO:0000305|PubMed:19099550}.
CC   -!- SIMILARITY: Belongs to the glutamate--cysteine ligase type 2 family.
CC       EgtA subfamily. {ECO:0000305}.
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DR   EMBL; AL123456; CCP46529.1; -; Genomic_DNA.
DR   PIR; A70794; A70794.
DR   RefSeq; NP_218221.1; NC_000962.3.
DR   RefSeq; WP_003419809.1; NZ_NVQJ01000028.1.
DR   AlphaFoldDB; P9WPK7; -.
DR   SMR; P9WPK7; -.
DR   STRING; 83332.Rv3704c; -.
DR   PaxDb; P9WPK7; -.
DR   DNASU; 885053; -.
DR   GeneID; 885053; -.
DR   KEGG; mtu:Rv3704c; -.
DR   TubercuList; Rv3704c; -.
DR   eggNOG; COG3572; Bacteria.
DR   OMA; GLTFREW; -.
DR   PhylomeDB; P9WPK7; -.
DR   UniPathway; UPA01014; -.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0004357; F:glutamate-cysteine ligase activity; IDA:UniProtKB.
DR   GO; GO:0052699; P:ergothioneine biosynthetic process; IEA:UniProtKB-UniRule.
DR   GO; GO:0006750; P:glutathione biosynthetic process; IEA:InterPro.
DR   HAMAP; MF_02034; EgtA; 1.
DR   InterPro; IPR017809; EgtA_Actinobacteria.
DR   InterPro; IPR035434; GCL_bact_plant.
DR   InterPro; IPR006336; GCS2.
DR   InterPro; IPR014746; Gln_synth/guanido_kin_cat_dom.
DR   InterPro; IPR011556; Glut_cys_lig_pln_type.
DR   PANTHER; PTHR34378; PTHR34378; 1.
DR   PANTHER; PTHR34378:SF1; PTHR34378:SF1; 1.
DR   Pfam; PF04107; GCS2; 1.
DR   PIRSF; PIRSF017901; GCL; 1.
DR   SUPFAM; SSF55931; SSF55931; 1.
DR   TIGRFAMs; TIGR03444; EgtA_Cys_ligase; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Direct protein sequencing; Ligase; Nucleotide-binding;
KW   Reference proteome.
FT   CHAIN           1..432
FT                   /note="Glutamate--cysteine ligase EgtA"
FT                   /id="PRO_0000413646"
SQ   SEQUENCE   432 AA;  45795 MW;  FACD5FDFAACC44FD CRC64;
     MTLAAMTAAA SQLDNAAPDD VEITDSSAAA EYIADGCLVD GPLGRVGLEM EAHCFDPADP
     FRRPSWEEIT EVLEWLSPLP GGSVVSVEPG GAVELSGPPA DGVLAAIGAM TRDQAVLRSA
     LANAGLGLVF LGADPLRSPV RVNPGARYRA MEQFFAASHS GVPGAAMMTS TAAIQVNLDA
     GPQEGWAERV RLAHALGPTM IAIAANSPML GGRFSGWQST RQRVWGQMDS ARCGPILGAS
     GDHPGIDWAK YALKAPVMMV RSPDTQDTRA VTDYVPFTDW VDGRVLLDGR RATVADLVYH
     LTTLFPPVRP RQWLEIRYLD SVPDEVWPAV VFTLVTLLDD PVAADLAVDA VEPVATAWDT
     AARIGLADRR LYLAANRCLA IAARRVPTEL IGAMQRLVDH VDRGVCPADD FSDRVIAGGI
     ASAVTGMMHG AS