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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

  1. ATP binding Source: UniProtKB-KW
  2. glutathionylspermidine synthase activity Source: UniProtKB
  3. metal ion binding Source: UniProtKB-KW
  4. trypanothione synthase activity Source: UniProtKB

GO - Biological processi

  1. 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

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...

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: April 1, 2015
This is version 57 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.