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Protein

Trypanothione synthetase

Gene

TRS

Organism
Trypanosoma cruzi (strain CL Brener)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Bifunctional enzyme which catalyzes the formation of trypanothione (N1,N(8)-bis(glutathionyl)spermidine) from glutathione and spermidine. Converts spermidine or glutathionylspermidine into trypanothione. Can also convert aminopropylcadaverine into glutothionylaminopropylcadaverine and homotrypanothione. Also has low amidase activity, hydrolyzing trypanothione, homotrypanothione or glutathionylspermidine to form glutathione and the corresponding polyamine.1 Publication

Catalytic activityi

Glutathione + spermidine + ATP = glutathionylspermidine + ADP + phosphate.1 Publication
Glutathione + glutathionylspermidine + ATP = N1,N(8)-bis(glutathionyl)spermidine + ADP + phosphate.1 Publication

Enzyme regulationi

Subject to high-substrate inhibition by glutathione.1 Publication

Kineticsi

  1. KM=570 µM for glutathione with spermidine as cosubstrate1 Publication
  2. KM=190 µM for glutathione with glutathionylspermidine as cosubstrate1 Publication
  3. KM=53 µM for MgATP1 Publication
  4. KM=625 µM for spermidine1 Publication
  5. KM=662 µM for aminopropylcadaverine1 Publication
  6. KM=66 µM for glutathionylspermidine1 Publication

    pH dependencei

    Optimum pH is 8.1 with spermidine as substrate. Optimum pH is 8.5 with glutathionylspermidine as substrate.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei316 – 3161Transition state stabilizerBy similarity
    Metal bindingi318 – 3181Magnesium 1By similarity
    Metal bindingi332 – 3321Magnesium 1By similarity
    Metal bindingi332 – 3321Magnesium 2By similarity
    Metal bindingi334 – 3341Magnesium 2By similarity
    Binding sitei501 – 5011ATPBy similarity
    Binding sitei536 – 5361ATPBy similarity
    Binding sitei543 – 5431ATP; via amide nitrogenBy similarity
    Binding sitei571 – 5711ATPBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi316 – 3183ATPBy similarity
    Nucleotide bindingi606 – 6083ATPBy similarity

    GO - Molecular functioni

    • ATP binding Source: UniProtKB-KW
    • glutathionylspermidine synthase activity Source: UniProtKB
    • metal ion binding Source: UniProtKB-KW
    • trypanothione synthase activity Source: UniProtKB

    GO - Biological processi

    • trypanothione biosynthetic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Ligase

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi6.3.1.9. 6524.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Trypanothione synthetaseImported (EC:6.3.1.9)
    Gene namesi
    Name:TRSImported
    Synonyms:TrySImported
    ORF Names:Tc00.1047053509099.50, Tc00.1047053509319.90
    OrganismiTrypanosoma cruzi (strain CL Brener)
    Taxonomic identifieri353153 [NCBI]
    Taxonomic lineageiEukaryotaEuglenozoaKinetoplastidaTrypanosomatidaeTrypanosomaSchizotrypanum
    ProteomesiUP000002296 Componenti: Unassembled WGS sequence

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 647647Trypanothione synthetasePRO_0000403111Add
    BLAST

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Protein-protein interaction databases

    STRINGi353153.XP_810600.1.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9GT49.
    SMRiQ9GT49. Positions 8-620.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini26 – 166141Peptidase C51PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    In the C-terminal section; belongs to the glutathionylspermidine synthase preATP-grasp family.Curated
    Contains 1 peptidase C51 domain.PROSITE-ProRule annotation

    Phylogenomic databases

    KOiK01833.

    Family and domain databases

    InterProiIPR007921. CHAP_dom.
    IPR005494. GSPS_pre-ATP-grasp-like_dom.
    IPR016185. PreATP-grasp_dom.
    [Graphical view]
    PfamiPF05257. CHAP. 1 hit.
    PF03738. GSP_synth. 1 hit.
    [Graphical view]
    SUPFAMiSSF52440. SSF52440. 1 hit.
    PROSITEiPS50911. CHAP. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9GT49-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MPTLQSLAVP FGCVQGYAPG GIPAYSNKHE SYFSGERSID GNLFCGFKYQ
    60 70 80 90 100
    CVEFARRWLF ERKSLVLPDV DWAVHIFNLK EVSDARTGKP VRCVAIRNGT
    110 120 130 140 150
    AAKPVVDSLL IYPSDDYSPV GHVAAITEVG DKWVRIADQN HRFHKWDANY
    160 170 180 190 200
    AAELPLIHEK GVWTILDPLE DEVLKPLGWV TFPDTPDRNP NEPLVLHESL
    210 220 230 240 250
    HFKRGELPTL RRLTFTPTSR EKDWLDLTNE AEAYFADVCG IDVKNPKLEK
    260 270 280 290 300
    ASYYQMNREL YLDCAKYGNQ LHQMFLEATK FVLGSDELLR LFCIPEEYWP
    310 320 330 340 350
    RLRHSWETQP HAITGRFDFA FDEDTQQFKC FEYNADSAST LLECGVIQQK
    360 370 380 390 400
    WARSVGLDDG TTYSSGSLVS SRLQLAWEMA EVTGRVHFLI DNDDEEHYTA
    410 420 430 440 450
    LYVMQHASAA GLETKLCVLF DEFHFDENGV VVDSDGVAVT TVWKTWMWET
    460 470 480 490 500
    AIADHQKARV QRGNDWRPTP KDEVRLCDIL LGPNWDLRVF EPMWKIIPSN
    510 520 530 540 550
    KAILPIIYNK HPDHPALLRA SYELTVELQR TGYVRKPIVG RVGRNVTVTE
    560 570 580 590 600
    ASGDIAAKSD GDFSDRDMVY QELFRLPERD GYYAILGGWV IGDVYCGTGV
    610 620 630 640
    REDKTIITGL ESPFSALRVY QGAQRRPLTH EDLDKAEAAA VGGGLKT
    Length:647
    Mass (Da):73,458
    Last modified:March 1, 2001 - v1
    Checksum:iCA8C76ACD0D90F24
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti2 – 21P → T in strain: Silvio X10/7. 1 Publication
    Natural varianti5 – 51Q → K in strain: Silvio X10/7. 1 Publication
    Natural varianti71 – 711D → E in allele TRS-2. 1 Publication
    Natural varianti89 – 891K → Q in allele TRS-2 and strain Silvio X10/7. 2 Publications
    Natural varianti90 – 901P → N in allele TRS-2. 1 Publication
    Natural varianti106 – 1061V → A in allele TRS-2. 1 Publication
    Natural varianti132 – 1321K → N in allele TRS-2. 1 Publication
    Natural varianti175 – 1751K → R in allele TRS-2. 1 Publication
    Natural varianti184 – 1841D → E in allele TRS-2 and strain Silvio X10/7. 2 Publications
    Natural varianti207 – 2071L → V in allele TRS-2 and strain Silvio X10/7. 2 Publications
    Natural varianti218 – 2181T → N in allele TRS-2 and strain Silvio X10/7. 2 Publications
    Natural varianti237 – 2371D → G in strain: Silvio X10/7. 1 Publication
    Natural varianti237 – 2371D → S in allele TRS-2. 1 Publication
    Natural varianti248 – 2481L → V in allele TRS-2 and strain Silvio X10/7. 2 Publications
    Natural varianti265 – 2651A → T in allele TRS-2. 1 Publication
    Natural varianti265 – 2651A → V in strain: Silvio X10/7. 1 Publication
    Natural varianti283 – 2831L → I in allele TRS-2 and strain Silvio X10/7. 2 Publications
    Natural varianti288 – 2881L → Q in allele TRS-2 and strain Silvio X10/7. 2 Publications
    Natural varianti291 – 2911L → V in allele TRS-2. 1 Publication
    Natural varianti293 – 2931C → H in allele TRS-2 and strain Silvio X10/7. 2 Publications
    Natural varianti304 – 3052HS → YL in strain: Silvio X10/7. 1 Publication
    Natural varianti365 – 3651S → C in allele TRS-2. 1 Publication
    Natural varianti369 – 3691V → I in allele TRS-2 and strain Silvio X10/7. 2 Publications
    Natural varianti381 – 3811E → G in strain: Silvio X10/7. 1 Publication
    Natural varianti392 – 3921N → K in allele TRS-2 and strain Silvio X10/7. 2 Publications
    Natural varianti397 – 3971H → Y in allele TRS-2 and strain Silvio X10/7. 2 Publications
    Natural varianti487 – 4871L → M in strain: Silvio X10/7. 1 Publication
    Natural varianti498 – 4981P → S in strain: Silvio X10/7. 1 Publication
    Natural varianti526 – 5261V → I in strain: Silvio X10/7. 1 Publication
    Natural varianti535 – 5351R → K in allele TRS-2 and strain Silvio X10/7. 2 Publications
    Natural varianti562 – 5621D → N in allele TRS-2 and strain Silvio X10/7. 2 Publications
    Natural varianti564 – 5641S → L in strain: Silvio X10/7. 1 Publication
    Natural varianti604 – 6041K → T in strain: Silvio X10/7. 1 Publication
    Natural varianti615 – 6151S → I in allele TRS-2. 1 Publication
    Natural varianti615 – 6151S → R in strain: Silvio X10/7. 1 Publication
    Natural varianti624 – 6241Q → P in allele TRS-2. 1 Publication
    Natural varianti635 – 6351K → N in strain: Silvio X10/7. 1 Publication

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF311782 Genomic DNA. Translation: AAL26803.1.
    AF283000 Genomic DNA. Translation: AAG15408.1.
    AF283001 Genomic DNA. Translation: AAG15409.1.
    AY155571 Genomic DNA. Translation: AAO00722.1.
    AAHK01000291 Genomic DNA. Translation: EAN94225.1.
    AAHK01000838 Genomic DNA. Translation: EAN88749.1.
    RefSeqiXP_810600.1. XM_805507.1.
    XP_816076.1. XM_810983.1.

    Genome annotation databases

    GeneIDi3541408.
    3547898.
    KEGGitcr:509099.50.
    tcr:509319.90.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF311782 Genomic DNA. Translation: AAL26803.1.
    AF283000 Genomic DNA. Translation: AAG15408.1.
    AF283001 Genomic DNA. Translation: AAG15409.1.
    AY155571 Genomic DNA. Translation: AAO00722.1.
    AAHK01000291 Genomic DNA. Translation: EAN94225.1.
    AAHK01000838 Genomic DNA. Translation: EAN88749.1.
    RefSeqiXP_810600.1. XM_805507.1.
    XP_816076.1. XM_810983.1.

    3D structure databases

    ProteinModelPortaliQ9GT49.
    SMRiQ9GT49. Positions 8-620.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi353153.XP_810600.1.

    Chemistry

    BindingDBiQ9GT49.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    GeneIDi3541408.
    3547898.
    KEGGitcr:509099.50.
    tcr:509319.90.

    Phylogenomic databases

    KOiK01833.

    Enzyme and pathway databases

    BRENDAi6.3.1.9. 6524.

    Family and domain databases

    InterProiIPR007921. CHAP_dom.
    IPR005494. GSPS_pre-ATP-grasp-like_dom.
    IPR016185. PreATP-grasp_dom.
    [Graphical view]
    PfamiPF05257. CHAP. 1 hit.
    PF03738. GSP_synth. 1 hit.
    [Graphical view]
    SUPFAMiSSF52440. SSF52440. 1 hit.
    PROSITEiPS50911. CHAP. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "A single enzyme catalyses formation of Trypanothione from glutathione and spermidine in Trypanosoma cruzi."
      Oza S.L., Tetaud E., Ariyanayagam M.R., Warnon S.S., Fairlamb A.H.
      J. Biol. Chem. 277:35853-35861(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, SUBUNIT.
      Strain: Silvio X10/71 Publication.
    2. "Trypanothione synthetase locus in Trypanosoma cruzi CL Brener strain shows an extensive allelic divergence."
      Tran A.N., Andersson B., Pettersson U., Aslund L.
      Acta Trop. 87:269-278(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELES TRS-1 AND TRS-2), POLYMORPHISM.
      Strain: CL BrenerImported.
    3. "Trypanosoma cruzi (Tulahuen 0): expression, purification and functional characterization of an enzyme catalyzing trypanothione synthesis."
      Comini M.A., Salame M., Menge U., Martinez R., Miglieta H., Claus J.D., Guerrero S.A., Flohe L.
      Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE TRS-1).
      Strain: Tulahuen 0.
    4. "The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease."
      El-Sayed N.M.A., Myler P.J., Bartholomeu D.C., Nilsson D., Aggarwal G., Tran A.-N., Ghedin E., Worthey E.A., Delcher A.L., Blandin G., Westenberger S.J., Caler E., Cerqueira G.C., Branche C., Haas B., Anupama A., Arner E., Aslund L.
      , Attipoe P., Bontempi E., Bringaud F., Burton P., Cadag E., Campbell D.A., Carrington M., Crabtree J., Darban H., da Silveira J.F., de Jong P., Edwards K., Englund P.T., Fazelina G., Feldblyum T., Ferella M., Frasch A.C., Gull K., Horn D., Hou L., Huang Y., Kindlund E., Klingbeil M., Kluge S., Koo H., Lacerda D., Levin M.J., Lorenzi H., Louie T., Machado C.R., McCulloch R., McKenna A., Mizuno Y., Mottram J.C., Nelson S., Ochaya S., Osoegawa K., Pai G., Parsons M., Pentony M., Pettersson U., Pop M., Ramirez J.L., Rinta J., Robertson L., Salzberg S.L., Sanchez D.O., Seyler A., Sharma R., Shetty J., Simpson A.J., Sisk E., Tammi M.T., Tarleton R., Teixeira S., Van Aken S., Vogt C., Ward P.N., Wickstead B., Wortman J., White O., Fraser C.M., Stuart K.D., Andersson B.
      Science 309:409-415(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELES TRS-1 AND TRS-2).
      Strain: CL Brener.

    Entry informationi

    Entry nameiTRYS_TRYCC
    AccessioniPrimary (citable) accession number: Q9GT49
    Secondary accession number(s): Q95WL5, Q9GT48
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 11, 2011
    Last sequence update: March 1, 2001
    Last modified: June 24, 2015
    This is version 58 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Multifunctional enzyme, Reference proteome

    Documents

    1. Peptidase families
      Classification of peptidase families and list of entries
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.