ID GSHAB_CLOPE Reviewed; 778 AA. AC Q8XK30; DT 30-AUG-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2002, sequence version 1. DT 27-MAR-2024, entry version 121. 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}; GN OrderedLocusNames=CPE1573; OS Clostridium perfringens (strain 13 / Type A). OC Bacteria; Bacillota; Clostridia; Eubacteriales; Clostridiaceae; OC Clostridium. OX NCBI_TaxID=195102; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=13 / Type A; RX PubMed=11792842; DOI=10.1073/pnas.022493799; RA Shimizu T., Ohtani K., Hirakawa H., Ohshima K., Yamashita A., Shiba T., RA Ogasawara N., Hattori M., Kuhara S., Hayashi H.; RT "Complete genome sequence of Clostridium perfringens, an anaerobic flesh- RT eater."; RL Proc. Natl. Acad. Sci. U.S.A. 99:996-1001(2002). CC -!- FUNCTION: Synthesizes glutathione from L-glutamate and L-cysteine via CC gamma-L-glutamyl-L-cysteine. {ECO:0000255|HAMAP-Rule:MF_00782}. 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 -!- 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:0000255|HAMAP-Rule:MF_00782}. CC -!- SIMILARITY: In the N-terminal section; belongs to the CC glutamate--cysteine ligase type 1 family. Type 2 subfamily. CC {ECO:0000255|HAMAP-Rule:MF_00782}. 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; BA000016; BAB81279.1; -; Genomic_DNA. DR RefSeq; WP_011010516.1; NC_003366.1. DR AlphaFoldDB; Q8XK30; -. DR SMR; Q8XK30; -. DR STRING; 195102.gene:10490837; -. DR KEGG; cpe:CPE1573; -. DR HOGENOM; CLU_020728_1_0_9; -. DR UniPathway; UPA00142; UER00209. DR UniPathway; UPA00142; UER00210. DR Proteomes; UP000000818; 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 Gene3D; 3.30.590.20; -; 1. DR Gene3D; 3.30.1490.20; ATP-grasp fold, A domain; 1. DR Gene3D; 3.30.470.20; ATP-grasp fold, B domain; 2. DR HAMAP; MF_00782; Glut_biosynth; 1. DR InterPro; IPR011761; ATP-grasp. DR InterPro; IPR013815; ATP_grasp_subdomain_1. 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 NCBIfam; TIGR01435; glu_cys_lig_rel; 1. DR PANTHER; PTHR38761; GLUTAMATE--CYSTEINE LIGASE; 1. DR PANTHER; PTHR38761:SF1; GLUTAMATE--CYSTEINE LIGASE; 1. DR Pfam; PF18419; ATP-grasp_6; 1. DR Pfam; PF04262; Glu_cys_ligase; 1. DR SUPFAM; SSF55931; Glutamine synthetase/guanido kinase; 1. DR SUPFAM; SSF56059; Glutathione synthetase ATP-binding domain-like; 1. DR PROSITE; PS50975; ATP_GRASP; 1. PE 3: Inferred from homology; KW ATP-binding; Glutathione biosynthesis; Ligase; Magnesium; Manganese; KW Metal-binding; Multifunctional enzyme; Nucleotide-binding; KW Reference proteome. FT CHAIN 1..778 FT /note="Glutathione biosynthesis bifunctional protein GshAB" FT /id="PRO_0000192549" FT DOMAIN 521..777 FT /note="ATP-grasp" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782" FT REGION 1..354 FT /note="Glutamate--cysteine ligase" FT BINDING 548..606 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782" FT BINDING 728 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782" FT BINDING 728 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782" FT BINDING 747 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782" FT BINDING 747 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782" FT BINDING 747 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782" FT BINDING 747 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782" FT BINDING 749 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782" FT BINDING 749 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00782" SQ SEQUENCE 778 AA; 90463 MW; 2008FF46AF06423E CRC64; MVNLDKGLLK IIKDESLEDY FIKANFGLEK ENVRVTESGN LALTPHPKAF GDREKNAYIK TDFSESQLEM VTPVCNTLEE VYSFICNLNK VVSLEIMKNG EFLWPQSNPP ILPREEEIPI AKLSNREDEL YRENLSYKYG KKKQVISGIH YNFSFKEEFI KLLYKELKVE KDFREFKDDI YLRMARNFQK YHWLLIYLTG ASPVFHESYI EEIKEEGEKL GEDSYYIKDD TSLRNSSYGY KNKKDYYVSY NSIEEYASDI KNLVKDKEIQ SIKEYYNPIR LKSLGSEDML ESLLHKGIDY LEVRLLDLDP LSIQGVSKET LYLLHLFMIY TLLKENKEIT YKDQEEFFKN HDMVALKGRN EEAVIYENGV PVLLKDKGRE ILSEMDEIVE ILFSNNEEFK NVIKRALEKI NNPHDTISEK LIKDIKEEGY INFHMRLAKE YLNNFKNKEF NLVGYEDLEL STQILILDAI KRGIEFNIMD RLENFISLSD GEKVEYVKQA TKTSKDSYIT ALIMENKLVT KDILRENNIR VPKGKDYDNI DEAKKDFRLF KDEKIVIKPK STNFGLGISI FPGEYSREDY DKAVEIAFRE DSSILIEEFM TGKEYRFLVI GEEVVGILHR EPANVIGNGE STIEELVSEK NKDPLRGKGY KTPLEKIKLG EIEEMFLKNQ GLSFKSIPKN GEKIYLRENS NISTGGDSID FTDKIHPSYK EVALKSAKAV KALICGVDMV IDNIEEEAKE KNHGIIELNF NPAIHIHCFP YKGENRKAGE KILDLLFN //