GSHAB_STRA5
ID GSHAB_STRA5 Reviewed; 750 AA.
AC Q8DXM9;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Glutathione biosynthesis bifunctional protein GshAB {ECO:0000255|HAMAP-Rule:MF_00782};
DE AltName: Full=Gamma-GCS-GS {ECO:0000255|HAMAP-Rule:MF_00782};
DE Short=GCS-GS {ECO:0000255|HAMAP-Rule:MF_00782};
DE Includes:
DE RecName: Full=Glutamate--cysteine ligase {ECO:0000255|HAMAP-Rule:MF_00782};
DE EC=6.3.2.2 {ECO:0000255|HAMAP-Rule:MF_00782};
DE AltName: Full=Gamma-ECS {ECO:0000255|HAMAP-Rule:MF_00782};
DE Short=GCS {ECO:0000255|HAMAP-Rule:MF_00782};
DE AltName: Full=Gamma-glutamylcysteine synthetase {ECO:0000255|HAMAP-Rule:MF_00782};
DE Includes:
DE RecName: Full=Glutathione synthetase {ECO:0000255|HAMAP-Rule:MF_00782};
DE EC=6.3.2.3 {ECO:0000255|HAMAP-Rule:MF_00782};
DE AltName: Full=GSH synthetase {ECO:0000255|HAMAP-Rule:MF_00782};
DE Short=GS {ECO:0000255|HAMAP-Rule:MF_00782};
DE Short=GSH-S {ECO:0000255|HAMAP-Rule:MF_00782};
DE Short=GSHase {ECO:0000255|HAMAP-Rule:MF_00782};
DE AltName: Full=Glutathione synthase {ECO:0000255|HAMAP-Rule:MF_00782};
GN Name=gshAB {ECO:0000255|HAMAP-Rule:MF_00782};
GN Synonyms=gshF {ECO:0000255|HAMAP-Rule:MF_00782}; OrderedLocusNames=SAG1821;
OS Streptococcus agalactiae serotype V (strain ATCC BAA-611 / 2603 V/R).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=208435;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-611 / 2603 V/R;
RX PubMed=12200547; DOI=10.1073/pnas.182380799;
RA Tettelin H., Masignani V., Cieslewicz M.J., Eisen J.A., Peterson S.N.,
RA Wessels M.R., Paulsen I.T., Nelson K.E., Margarit I., Read T.D.,
RA Madoff L.C., Wolf A.M., Beanan M.J., Brinkac L.M., Daugherty S.C.,
RA DeBoy R.T., Durkin A.S., Kolonay J.F., Madupu R., Lewis M.R., Radune D.,
RA Fedorova N.B., Scanlan D., Khouri H.M., Mulligan S., Carty H.A.,
RA Cline R.T., Van Aken S.E., Gill J., Scarselli M., Mora M., Iacobini E.T.,
RA Brettoni C., Galli G., Mariani M., Vegni F., Maione D., Rinaudo D.,
RA Rappuoli R., Telford J.L., Kasper D.L., Grandi G., Fraser C.M.;
RT "Complete genome sequence and comparative genomic analysis of an emerging
RT human pathogen, serotype V Streptococcus agalactiae.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:12391-12396(2002).
RN [2]
RP CHARACTERIZATION.
RC STRAIN=ATCC BAA-611 / 2603 V/R;
RX PubMed=15642737; DOI=10.1074/jbc.m414326200;
RA Janowiak B.E., Griffith O.W.;
RT "Glutathione synthesis in Streptococcus agalactiae. One protein accounts
RT for gamma-glutamylcysteine synthetase and glutathione synthetase
RT activities.";
RL J. Biol. Chem. 280:11829-11839(2005).
CC -!- FUNCTION: Synthesizes glutathione from L-glutamate and L-cysteine via
CC gamma-L-glutamyl-L-cysteine.
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:0000255|HAMAP-Rule:MF_00782};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + gamma-L-glutamyl-L-cysteine + glycine = ADP +
CC glutathione + H(+) + phosphate; Xref=Rhea:RHEA:13557,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:57925, ChEBI:CHEBI:58173,
CC ChEBI:CHEBI:456216; EC=6.3.2.3; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_00782};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 2 magnesium or manganese ions per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by L-buthionine-S-sulfoximine (L-S-BSO).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=22 mM for L-glutamate;
CC KM=156 uM for L-cysteine;
CC KM=8.2 mM for alpha-L-aminobutyrate;
CC KM=64 uM for ATP (in the reaction with gamma-GCS);
CC KM=5.9 mM for gamma-L-glutamyl-L-cysteine;
CC KM=11.5 mM for gamma-L-glutamyl-L-alpha-aminobutyrate;
CC KM=6.3 mM for glycine;
CC KM=420 uM for ATP (in the reaction with GS);
CC -!- PATHWAY: Sulfur metabolism; glutathione biosynthesis; glutathione from
CC L-cysteine and L-glutamate: step 1/2. {ECO:0000255|HAMAP-
CC Rule:MF_00782}.
CC -!- PATHWAY: Sulfur metabolism; glutathione biosynthesis; glutathione from
CC L-cysteine and L-glutamate: step 2/2. {ECO:0000255|HAMAP-
CC Rule:MF_00782}.
CC -!- SUBUNIT: Monomer. {ECO:0000305}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the glutamate--
CC cysteine ligase type 1 family. Type 2 subfamily. {ECO:0000255|HAMAP-
CC Rule:MF_00782}.
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DR EMBL; AE009948; AAN00684.1; -; Genomic_DNA.
DR RefSeq; NP_688811.1; NC_004116.1.
DR RefSeq; WP_000582678.1; NC_004116.1.
DR PDB; 3LN6; X-ray; 2.95 A; A=1-750.
DR PDBsum; 3LN6; -.
DR AlphaFoldDB; Q8DXM9; -.
DR SMR; Q8DXM9; -.
DR STRING; 208435.SAG1821; -.
DR EnsemblBacteria; AAN00684; AAN00684; SAG1821.
DR KEGG; sag:SAG1821; -.
DR PATRIC; fig|208435.3.peg.1829; -.
DR HOGENOM; CLU_020728_1_0_9; -.
DR OMA; EANFNPM; -.
DR BRENDA; 6.3.2.2; 15082.
DR BRENDA; 6.3.2.3; 5917.
DR SABIO-RK; Q8DXM9; -.
DR UniPathway; UPA00142; UER00209.
DR UniPathway; UPA00142; UER00210.
DR Proteomes; UP000000821; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004357; F:glutamate-cysteine ligase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0004363; F:glutathione synthase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR HAMAP; MF_00782; Glut_biosynth; 1.
DR InterPro; IPR011761; ATP-grasp.
DR InterPro; IPR014746; Gln_synth/guanido_kin_cat_dom.
DR InterPro; IPR007370; Glu_cys_ligase.
DR InterPro; IPR006335; Glut_biosynth.
DR InterPro; IPR006334; Glut_cys_ligase.
DR InterPro; IPR040657; GshAB_ATP-grasp.
DR InterPro; IPR020561; PRibGlycinamid_synth_ATP-grasp.
DR PANTHER; PTHR38761; PTHR38761; 1.
DR Pfam; PF18419; ATP-grasp_6; 1.
DR Pfam; PF01071; GARS_A; 1.
DR Pfam; PF04262; Glu_cys_ligase; 2.
DR SUPFAM; SSF55931; SSF55931; 1.
DR TIGRFAMs; TIGR01435; glu_cys_lig_rel; 1.
DR PROSITE; PS50975; ATP_GRASP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Glutathione biosynthesis; Ligase; Magnesium;
KW Manganese; Metal-binding; Multifunctional enzyme; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..750
FT /note="Glutathione biosynthesis bifunctional protein GshAB"
FT /id="PRO_0000192559"
FT DOMAIN 489..747
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782"
FT REGION 1..333
FT /note="Glutamate--cysteine ligase"
FT REGION 32..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 516..574
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782"
FT BINDING 696
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782"
FT BINDING 696
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782"
FT BINDING 717
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782"
FT BINDING 717
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782"
FT BINDING 717
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782"
FT BINDING 717
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782"
FT BINDING 719
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782"
FT BINDING 719
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782"
FT HELIX 7..9
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 19..31
FT /evidence="ECO:0007829|PDB:3LN6"
FT TURN 32..35
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:3LN6"
FT TURN 49..51
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 53..67
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 74..91
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:3LN6"
FT TURN 109..111
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 120..133
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 136..139
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 143..149
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 151..161
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 166..191
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:3LN6"
FT TURN 206..208
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 234..243
FT /evidence="ECO:0007829|PDB:3LN6"
FT TURN 246..248
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 253..255
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 259..264
FT /evidence="ECO:0007829|PDB:3LN6"
FT TURN 268..274
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 278..281
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 296..311
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 318..334
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 347..361
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 365..379
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 385..392
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 399..413
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 421..423
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 428..440
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 443..447
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 449..451
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 453..458
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 461..466
FT /evidence="ECO:0007829|PDB:3LN6"
FT TURN 467..469
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 477..481
FT /evidence="ECO:0007829|PDB:3LN6"
FT TURN 482..484
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 486..494
FT /evidence="ECO:0007829|PDB:3LN6"
FT TURN 507..510
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 511..517
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 518..521
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 523..527
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 532..535
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 537..541
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 545..558
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 560..566
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 570..578
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 581..589
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 592..594
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 601..608
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 614..618
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 621..623
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 629..637
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 651..654
FT /evidence="ECO:0007829|PDB:3LN6"
FT TURN 660..663
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 665..668
FT /evidence="ECO:0007829|PDB:3LN6"
FT TURN 670..672
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 675..687
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 694..700
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 702..704
FT /evidence="ECO:0007829|PDB:3LN6"
FT TURN 708..711
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 714..721
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 725..728
FT /evidence="ECO:0007829|PDB:3LN6"
FT STRAND 731..733
FT /evidence="ECO:0007829|PDB:3LN6"
FT HELIX 739..746
FT /evidence="ECO:0007829|PDB:3LN6"
SQ SEQUENCE 750 AA; 85603 MW; 97829C2C5B44174A CRC64;
MIIDRLLQRS HSHLPILQAT FGLERESLRI HQPTQRVAQT PHPKTLGSRN YHPYIQTDYS
EPQLELITPI AKDSQEAIRF LKAISDVAGR SINHDEYLWP LSMPPKVREE DIQIAQLEDA
FEYDYRKYLE KTYGKLIQSI SGIHYNLGLG QELLTSLFEL SQADNAIDFQ NQLYMKLSQN
FLRYRWLLTY LYGASPVAEE DFLDQKLNNP VRSLRNSHLG YVNHKDIRIS YTSLKDYVND
LENAVKSGQL IAEKEFYSPV RLRGSKACRN YLEKGITYLE FRTFDLNPFS PIGITQETVD
TVHLFLLALL WIDSSSHIDQ DIKEANRLND LIALSHPLEK LPNQAPVSDL VDAMQSVIQH
FNLSPYYQDL LESVKRQIQS PELTVAGQLL EMIEGLSLET FGQRQGQIYH DYAWEAPYAL
KGYETMELST QLLLFDVIQK GVNFEVLDEQ DQFLKLWHNS HIEYVKNGNM TSKDNYIVPL
AMANKVVTKK ILDEKHFPTP FGDEFTDRKE ALNYFSQIQD KPIVVKPKST NFGLGISIFK
TSANLASYEK AIDIAFTEDS AILVEEYIEG TEYRFFVLEG DCIAVLLRVA ANVVGDGIHT
ISQLVKLKNQ NPLRGYDHRS PLEVIELGEV EQLMLEQQGY TVNSIPPEGT KIELRRNSNI
STGGDSIDVT NTMDPTYKQL AAEMAEAMGA WVCGVDLIIP NATQAYSKDK KNATCIELNF
NPLMYMHTYC QEGPGQSITP RILAKLFPEL
