GLTB_MYCTU
ID GLTB_MYCTU Reviewed; 1527 AA.
AC P96218; F2GDM1; L0TDS2;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 3.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Glutamate synthase [NADPH] large chain;
DE EC=1.4.1.13;
DE AltName: Full=Glutamate synthase subunit alpha;
DE Short=GLTS alpha chain;
GN Name=gltB; OrderedLocusNames=Rv3859c;
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 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 [3]
RP ACTIVITY REGULATION, AND INTERACTION WITH GARA.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19318624; DOI=10.1126/scisignal.2000212;
RA Nott T.J., Kelly G., Stach L., Li J., Westcott S., Patel D., Hunt D.M.,
RA Howell S., Buxton R.S., O'Hare H.M., Smerdon S.J.;
RT "An intramolecular switch regulates phosphoindependent FHA domain
RT interactions in Mycobacterium tuberculosis.";
RL Sci. Signal. 2:RA12-RA12(2009).
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 -!- CATALYTIC ACTIVITY:
CC Reaction=2 L-glutamate + NADP(+) = 2-oxoglutarate + H(+) + L-glutamine
CC + NADPH; Xref=Rhea:RHEA:15501, ChEBI:CHEBI:15378, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:58359; EC=1.4.1.13;
CC -!- COFACTOR:
CC Name=[3Fe-4S] cluster; Xref=ChEBI:CHEBI:21137; Evidence={ECO:0000250};
CC Note=Binds 1 [3Fe-4S] cluster. {ECO:0000250};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Activity is stimulated by unphosphorylated GarA.
CC {ECO:0000269|PubMed:19318624}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-glutamate biosynthesis via GLT
CC pathway; L-glutamate from 2-oxoglutarate and L-glutamine (NADP(+)
CC route): step 1/1.
CC -!- SUBUNIT: Interacts with unphosphorylated GarA.
CC {ECO:0000269|PubMed:19318624}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the glutamate synthase family. {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; AL123456; CCP46688.1; -; Genomic_DNA.
DR PIR; H70655; H70655.
DR RefSeq; NP_218376.1; NC_000962.3.
DR RefSeq; WP_003899733.1; NZ_NVQJ01000057.1.
DR AlphaFoldDB; P96218; -.
DR SMR; P96218; -.
DR IntAct; P96218; 1.
DR STRING; 83332.Rv3859c; -.
DR PaxDb; P96218; -.
DR GeneID; 886195; -.
DR KEGG; mtu:Rv3859c; -.
DR TubercuList; Rv3859c; -.
DR eggNOG; COG0067; Bacteria.
DR eggNOG; COG0069; Bacteria.
DR eggNOG; COG0070; Bacteria.
DR InParanoid; P96218; -.
DR OMA; TVFRLQH; -.
DR PhylomeDB; P96218; -.
DR UniPathway; UPA00634; UER00689.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0051538; F:3 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0004355; F:glutamate synthase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0015930; F:glutamate synthase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0019676; P:ammonia assimilation cycle; IBA:GO_Central.
DR GO; GO:0006537; P:glutamate biosynthetic process; IBA:GO_Central.
DR GO; GO:0097054; P:L-glutamate biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00982; gltB_C; 1.
DR CDD; cd02808; GltS_FMN; 1.
DR Gene3D; 2.160.20.60; -; 1.
DR Gene3D; 3.20.20.70; -; 2.
DR Gene3D; 3.60.20.10; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR017932; GATase_2_dom.
DR InterPro; IPR002489; Glu_synth_asu_C.
DR InterPro; IPR036485; Glu_synth_asu_C_sf.
DR InterPro; IPR006982; Glu_synth_centr_N.
DR InterPro; IPR002932; Glu_synthdom.
DR InterPro; IPR029055; Ntn_hydrolases_N.
DR Pfam; PF00310; GATase_2; 1.
DR Pfam; PF04898; Glu_syn_central; 1.
DR Pfam; PF01645; Glu_synthase; 1.
DR Pfam; PF01493; GXGXG; 1.
DR SUPFAM; SSF56235; SSF56235; 1.
DR SUPFAM; SSF69336; SSF69336; 1.
DR PROSITE; PS51278; GATASE_TYPE_2; 1.
PE 1: Evidence at protein level;
KW 3Fe-4S; Amino-acid biosynthesis; FAD; Flavoprotein; FMN;
KW Glutamate biosynthesis; Glutamine amidotransferase; Iron; Iron-sulfur;
KW Metal-binding; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..1527
FT /note="Glutamate synthase [NADPH] large chain"
FT /id="PRO_0000419545"
FT DOMAIN 18..416
FT /note="Glutamine amidotransferase type-2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00609"
FT ACT_SITE 18
FT /note="For GATase activity"
FT /evidence="ECO:0000250"
FT BINDING 1083..1135
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 1136
FT /ligand="[3Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:21137"
FT /evidence="ECO:0000250"
FT BINDING 1142
FT /ligand="[3Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:21137"
FT /evidence="ECO:0000250"
FT BINDING 1147
FT /ligand="[3Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:21137"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1527 AA; 165943 MW; 7ADAB46904A3AE46 CRC64;
MTPKRVGLYN PAFEHDSCGV AMVVDMHGRR SRDIVDKAIT ALLNLEHRGA QGAEPRSGDG
AGILIQVPDE FLREAVDFEL PAPGSYATGI AFLPQSSKDA AAACAAVQKI AEAEGLQVLG
WRSVPTDDSS LGALSRDAMP TFRQVFLAGA SGMALERRCY VVRKRAEHEL GTKGPGQDGP
GRETVYFPSL SGQTLVYKGM LTTPQLKAFY LDLQDERLTS ALGIVHSRFS TNTFPSWPLA
HPFRRIAHNG EINTVTGNEN WMRAREALIK TDIFGSAADV EKLFPICTPG ASDTARFDEV
LELLHLGGRS LAHAVLMMIP EAWERHESMD PARRAFYQYH ASLMEPWDGP ASMTFTDGTV
VGAVLDRNGL RPSRIWVTDD GLVVMASEAG VLDLHPSTVV RRMRLQPGRM FLVDTAQGRI
VSDEEIKADL AAEHPYQEWL DNGLVPLDEL PEGKDVRMPH HRIVMRQLAF GYTYEELNLL
VAPMARLGAE PIGSMGTDTP VAVLSQRPRM LYDYFHQLFA QVTNPPLDAI REEVVTSLQG
TTGGERDLLN PDQNSCHQIV LPQPILRNHE LAKLVSLDPN DKVNGRPHGL RSKVIRCLYR
VSEGGAGLAA ALEEVRGAAA AAIADGARII ILSDRESDEE MAPIPSLLAV AGVHHHLVRE
RTRTQVGLVV ESGDAREVHH MAALVGFGAA AINPYLVFES IEDMLDRGVI EGIDRTAALN
NYIKAAGKGV LKVMSKMGIS TLASYTGAQL FQAVGISEQV LDEYFTGLTC PTGGITLDDI
AADVAARHRL AYLDRPDERA HRELEVGGEY QWRREGEYHL FNPETVFKLQ HSTRTGQYKI
FKEYTRLVDD QSERMASLRG LLKFRTGVRP PVPLDEVEPA SEIVKRFSTG AMSYGSISAE
AHETLAIAMN RLGARSNCGE GGEDVKRFDR DPNGDWRRSA IKQVASARFG VTSHYLTNCT
DLQIKMAQGA KPGEGGQLPG HKVYPWVAEV RHSTPGVGLI SPPPHHDIYS IEDLAQLIHD
LKNANPSARV HVKLVSENGV GTVAAGVSKA HADVVLISGH DGGTGATPLT SMKHAGAPWE
LGLAETQQTL LLNGLRDRIV VQVDGQLKTG RDVMIATLLG AEEFGFATAP LVVAGCIMMR
VCHLDTCPVG VATQNPLLRE RFTGKPEFVE NFFMFIAEEV REYLAQLGFR TVNEAVGQAG
ALDTTLARAH WKAHKLDLAP VLHEPESAFM NQDLYCSSRQ DHGLDKALDQ QLIVMSREAL
DSGKPVRFST TIGNVNRTVG TMLGHELTKA YGGQGLPDGT IDITFDGSAG NSFGAFVPKG
ITLRVYGDAN DYVGKGLSGG RIVVRPSDDA PQDYVAEDNI IGGNVILFGA TSGEVYLRGV
VGERFAVRNS GAHAVVEGVG DHGCEYMTGG RVVILGRTGR NFAAGMSGGV AYVYDPDGEL
PANLNSEMVE LETLDEDDAD WLHGTIQVHV DATDSAVGQR ILSDWSGQQR HFVKVMPRDY
KRVLQAIALA ERDGVDVDKA IMAAAHG
