GSP_SHIFL
ID GSP_SHIFL Reviewed; 619 AA.
AC P0AES1; P43675;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Bifunctional glutathionylspermidine synthetase/amidase;
DE Short=GspSA;
DE Includes:
DE RecName: Full=Glutathionylspermidine amidase;
DE Short=Gsp amidase;
DE EC=3.5.1.78 {ECO:0000250|UniProtKB:P0AES0};
DE AltName: Full=Glutathionylspermidine amidohydrolase [spermidine-forming];
DE Includes:
DE RecName: Full=Glutathionylspermidine synthetase;
DE Short=Gsp synthetase;
DE EC=6.3.1.8 {ECO:0000250|UniProtKB:P0AES0};
DE AltName: Full=Glutathione:spermidine ligase [ADP-forming];
DE AltName: Full=Gsp synthase;
GN Name=gss; Synonyms=gsp; OrderedLocusNames=SF3035, S3236;
OS Shigella flexneri.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Shigella.
OX NCBI_TaxID=623;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=301 / Serotype 2a;
RX PubMed=12384590; DOI=10.1093/nar/gkf566;
RA Jin Q., Yuan Z., Xu J., Wang Y., Shen Y., Lu W., Wang J., Liu H., Yang J.,
RA Yang F., Zhang X., Zhang J., Yang G., Wu H., Qu D., Dong J., Sun L.,
RA Xue Y., Zhao A., Gao Y., Zhu J., Kan B., Ding K., Chen S., Cheng H.,
RA Yao Z., He B., Chen R., Ma D., Qiang B., Wen Y., Hou Y., Yu J.;
RT "Genome sequence of Shigella flexneri 2a: insights into pathogenicity
RT through comparison with genomes of Escherichia coli K12 and O157.";
RL Nucleic Acids Res. 30:4432-4441(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700930 / 2457T / Serotype 2a;
RX PubMed=12704152; DOI=10.1128/iai.71.5.2775-2786.2003;
RA Wei J., Goldberg M.B., Burland V., Venkatesan M.M., Deng W., Fournier G.,
RA Mayhew G.F., Plunkett G. III, Rose D.J., Darling A., Mau B., Perna N.T.,
RA Payne S.M., Runyen-Janecky L.J., Zhou S., Schwartz D.C., Blattner F.R.;
RT "Complete genome sequence and comparative genomics of Shigella flexneri
RT serotype 2a strain 2457T.";
RL Infect. Immun. 71:2775-2786(2003).
CC -!- FUNCTION: Catalyzes the formation of an amide bond between glutathione
CC (GSH) and spermidine coupled with hydrolysis of ATP; also catalyzes the
CC opposing reaction, i.e. the hydrolysis of glutathionylspermidine (Gsp)
CC back to glutathione and spermidine. May act synergistically with
CC glutaredoxin to regulate the redox environment and defend against
CC oxidative damage. {ECO:0000250|UniProtKB:P0AES0}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glutathione + spermidine = ADP + glutathionylspermidine
CC + H(+) + phosphate; Xref=Rhea:RHEA:21272, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57834,
CC ChEBI:CHEBI:57835, ChEBI:CHEBI:57925, ChEBI:CHEBI:456216; EC=6.3.1.8;
CC Evidence={ECO:0000250|UniProtKB:P0AES0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutathionylspermidine + H2O = glutathione + spermidine;
CC Xref=Rhea:RHEA:17173, ChEBI:CHEBI:15377, ChEBI:CHEBI:57834,
CC ChEBI:CHEBI:57835, ChEBI:CHEBI:57925; EC=3.5.1.78;
CC Evidence={ECO:0000250|UniProtKB:P0AES0};
CC -!- ACTIVITY REGULATION: When exposed to oxidative stress, Gsp amidase
CC activity is transiently inhibited in vivo by oxidation of the catalytic
CC Cys-59 thiol to sulfenic acid; this modification does not affect Gsp
CC synthetase activity. {ECO:0000250|UniProtKB:P0AES0}.
CC -!- PATHWAY: Sulfur metabolism; glutathione metabolism.
CC -!- PATHWAY: Amine and polyamine metabolism; spermidine metabolism.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P0AES0}.
CC -!- DOMAIN: The two activities reside in distinct domains (N-terminal
CC amidase and C-terminal synthetase). The two domains expressed
CC independently are folded and functional (By similarity). {ECO:0000250}.
CC -!- PTM: Oxidation of Cys-59 to sulfenic acid during oxidative stress
CC selectively inhibits the amidase activity.
CC {ECO:0000250|UniProtKB:P0AES0}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the
CC glutathionylspermidine synthase preATP-grasp family. {ECO:0000305}.
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DR EMBL; AE005674; AAN44513.2; -; Genomic_DNA.
DR EMBL; AE014073; AAP18324.1; -; Genomic_DNA.
DR RefSeq; NP_708806.2; NC_004337.2.
DR RefSeq; WP_001297309.1; NZ_WPGW01000034.1.
DR AlphaFoldDB; P0AES1; -.
DR SMR; P0AES1; -.
DR STRING; 198214.SF3035; -.
DR EnsemblBacteria; AAN44513; AAN44513; SF3035.
DR EnsemblBacteria; AAP18324; AAP18324; S3236.
DR GeneID; 1026646; -.
DR GeneID; 66673115; -.
DR KEGG; sfl:SF3035; -.
DR KEGG; sfx:S3236; -.
DR PATRIC; fig|198214.7.peg.3609; -.
DR HOGENOM; CLU_478805_0_0_6; -.
DR OMA; YMGYKWQ; -.
DR OrthoDB; 692145at2; -.
DR UniPathway; UPA00204; -.
DR UniPathway; UPA00819; -.
DR Proteomes; UP000001006; Chromosome.
DR Proteomes; UP000002673; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008884; F:glutathionylspermidine amidase activity; IEA:UniProtKB-EC.
DR GO; GO:0008885; F:glutathionylspermidine synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006749; P:glutathione metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008216; P:spermidine metabolic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR007921; CHAP_dom.
DR InterPro; IPR005494; GSPS_pre-ATP-grasp-like_dom.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR016185; PreATP-grasp_dom_sf.
DR Pfam; PF05257; CHAP; 1.
DR Pfam; PF03738; GSP_synth; 1.
DR SUPFAM; SSF52440; SSF52440; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50911; CHAP; 1.
PE 3: Inferred from homology;
KW ATP-binding; Hydrolase; Ligase; Magnesium; Metal-binding;
KW Multifunctional enzyme; Nucleotide-binding; Oxidation; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250"
FT CHAIN 2..619
FT /note="Bifunctional glutathionylspermidine
FT synthetase/amidase"
FT /id="PRO_0000070444"
FT DOMAIN 34..176
FT /note="Peptidase C51"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00048"
FT REGION 2..195
FT /note="Gsp amidase"
FT REGION 196..205
FT /note="Linker"
FT REGION 206..619
FT /note="Gsp synthetase"
FT ACT_SITE 59
FT /note="S-(gamma-glutamyl-cysteinyl-glycyl)-cysteine
FT intermediate"
FT /evidence="ECO:0000250"
FT BINDING 58
FT /ligand="glutathionylspermidine"
FT /ligand_id="ChEBI:CHEBI:57835"
FT /evidence="ECO:0000250"
FT BINDING 64
FT /ligand="glutathionylspermidine"
FT /ligand_id="ChEBI:CHEBI:57835"
FT /evidence="ECO:0000250"
FT BINDING 78..81
FT /ligand="glutathionylspermidine"
FT /ligand_id="ChEBI:CHEBI:57835"
FT /evidence="ECO:0000250"
FT BINDING 149
FT /ligand="glutathionylspermidine"
FT /ligand_id="ChEBI:CHEBI:57835"
FT /evidence="ECO:0000250"
FT BINDING 316..318
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 316
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250"
FT BINDING 318
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 330
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 330
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 332
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 335
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250"
FT BINDING 391
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000250"
FT BINDING 392
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250"
FT BINDING 446
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250"
FT BINDING 498
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 533
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 539..540
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 568..571
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 582
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 603..605
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 610
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000250"
FT SITE 131
FT /note="Increases nucleophilicity of active site Cys; for
FT amidase activity"
FT /evidence="ECO:0000250"
FT SITE 316
FT /note="Transition state stabilizer; for synthetase
FT activity"
FT /evidence="ECO:0000250"
FT MOD_RES 59
FT /note="Cysteine sulfenic acid (-SOH); transient"
FT /evidence="ECO:0000250"
SQ SEQUENCE 619 AA; 70532 MW; 07FB43D8A0B2933C CRC64;
MSKGTTSQDA PFGTLLGYAP GGVAIYSSDY SSLDPQEYED DAVFRSYIDD EYMGHKWQCV
EFARRFLFLN YGVVFTDVGM AWEIFSLRFL REVVNDNILP LQAFPNGSPR APVAGALLIW
DKGGEFKDTG HVAIITQLHG NKVRIAEQNV IHSPLPQGQQ WTRELEMVVE NGCYTLKDTF
DDTTILGWMI QTEDTEYSLP QPEIAGELLK ISGARLENKG QFDGKWLDEK DPLQNAYVQA
NGQVINQDPY HYYTITESAE QELIKATNEL HLMYLHATDK VLKDDNLLAL FDIPKILWPR
LRLSWQRRRH HMITGRMDFC MDERGLKVYE YNADSASCHT EAGLILERWA EQGYKGNGFN
PAEGLINELA GAWKHSRARP FVHIMQDKDI EENYHAQFME QALHQAGFET RILRGLDELG
WDAAGQLIDG EGRLVNCVWK TWAWETAFDQ IREVSDREFA AVPIRTGHPQ NEVRLIDVLL
RPEVLVFEPL WTVIPGNKAI LPILWSLFPH HRYLLDTDFT VNDELVKTGY AVKPIAGRCG
SNIDLVSHHE EVLDKTSGKF AEQKNIYQQL WCLPKVDGKY IQVCTFTVGG NYGGTCLRGD
ESLVIKKESD IEPLIVVKK
