TRYS_TRYCC
ID TRYS_TRYCC Reviewed; 647 AA.
AC Q9GT49; Q95WL5; Q9GT48;
DT 11-JAN-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Trypanothione synthetase {ECO:0000312|EMBL:AAL26803.1};
DE EC=6.3.1.9;
GN Name=TRS {ECO:0000312|EMBL:AAG15409.1};
GN Synonyms=TryS {ECO:0000312|EMBL:AAL26803.1};
GN ORFNames=Tc00.1047053509099.50, Tc00.1047053509319.90;
OS Trypanosoma cruzi (strain CL Brener).
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma; Schizotrypanum.
OX NCBI_TaxID=353153;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAL26803.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND SUBUNIT.
RC STRAIN=Silvio X10/7 {ECO:0000269|PubMed:12121990};
RX PubMed=12121990; DOI=10.1074/jbc.m204403200;
RA Oza S.L., Tetaud E., Ariyanayagam M.R., Warnon S.S., Fairlamb A.H.;
RT "A single enzyme catalyses formation of Trypanothione from glutathione and
RT spermidine in Trypanosoma cruzi.";
RL J. Biol. Chem. 277:35853-35861(2002).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAG15409.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELES TRS-1 AND TRS-2), AND
RP POLYMORPHISM.
RC STRAIN=CL Brener {ECO:0000312|EMBL:AAG15409.1};
RX PubMed=12826302; DOI=10.1016/s0001-706x(03)00067-6;
RA Tran A.N., Andersson B., Pettersson U., Aslund L.;
RT "Trypanothione synthetase locus in Trypanosoma cruzi CL Brener strain shows
RT an extensive allelic divergence.";
RL Acta Trop. 87:269-278(2003).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAO00722.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE TRS-1).
RC STRAIN=Tulahuen 0;
RA Comini M.A., Salame M., Menge U., Martinez R., Miglieta H., Claus J.D.,
RA Guerrero S.A., Flohe L.;
RT "Trypanosoma cruzi (Tulahuen 0): expression, purification and functional
RT characterization of an enzyme catalyzing trypanothione synthesis.";
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELES TRS-1 AND TRS-2).
RC STRAIN=CL Brener;
RX PubMed=16020725; DOI=10.1126/science.1112631;
RA El-Sayed N.M.A., Myler P.J., Bartholomeu D.C., Nilsson D., Aggarwal G.,
RA Tran A.-N., Ghedin E., Worthey E.A., Delcher A.L., Blandin G.,
RA Westenberger S.J., Caler E., Cerqueira G.C., Branche C., Haas B.,
RA Anupama A., Arner E., Aslund L., Attipoe P., Bontempi E., Bringaud F.,
RA Burton P., Cadag E., Campbell D.A., Carrington M., Crabtree J., Darban H.,
RA da Silveira J.F., de Jong P., Edwards K., Englund P.T., Fazelina G.,
RA Feldblyum T., Ferella M., Frasch A.C., Gull K., Horn D., Hou L., Huang Y.,
RA Kindlund E., Klingbeil M., Kluge S., Koo H., Lacerda D., Levin M.J.,
RA Lorenzi H., Louie T., Machado C.R., McCulloch R., McKenna A., Mizuno Y.,
RA Mottram J.C., Nelson S., Ochaya S., Osoegawa K., Pai G., Parsons M.,
RA Pentony M., Pettersson U., Pop M., Ramirez J.L., Rinta J., Robertson L.,
RA Salzberg S.L., Sanchez D.O., Seyler A., Sharma R., Shetty J., Simpson A.J.,
RA Sisk E., Tammi M.T., Tarleton R., Teixeira S., Van Aken S., Vogt C.,
RA Ward P.N., Wickstead B., Wortman J., White O., Fraser C.M., Stuart K.D.,
RA Andersson B.;
RT "The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas
RT disease.";
RL Science 309:409-415(2005).
CC -!- FUNCTION: Bifunctional enzyme which catalyzes the formation of
CC trypanothione (N(1),N(8)-bis(glutathionyl)spermidine) from glutathione
CC and spermidine. Converts spermidine or glutathionylspermidine into
CC trypanothione. Can also convert aminopropylcadaverine into
CC glutothionylaminopropylcadaverine and homotrypanothione. Also has low
CC amidase activity, hydrolyzing trypanothione, homotrypanothione or
CC glutathionylspermidine to form glutathione and the corresponding
CC polyamine. {ECO:0000269|PubMed:12121990}.
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=6.3.1.9;
CC Evidence={ECO:0000269|PubMed:12121990};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glutathione + glutathionylspermidine = ADP + H(+) +
CC phosphate + trypanothione; Xref=Rhea:RHEA:21532, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57835,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:58290, ChEBI:CHEBI:456216; EC=6.3.1.9;
CC Evidence={ECO:0000269|PubMed:12121990};
CC -!- ACTIVITY REGULATION: Subject to high-substrate inhibition by
CC glutathione. {ECO:0000269|PubMed:12121990}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=570 uM for glutathione with spermidine as cosubstrate
CC {ECO:0000269|PubMed:12121990};
CC KM=190 uM for glutathione with glutathionylspermidine as cosubstrate
CC {ECO:0000269|PubMed:12121990};
CC KM=53 uM for MgATP {ECO:0000269|PubMed:12121990};
CC KM=625 uM for spermidine {ECO:0000269|PubMed:12121990};
CC KM=662 uM for aminopropylcadaverine {ECO:0000269|PubMed:12121990};
CC KM=66 uM for glutathionylspermidine {ECO:0000269|PubMed:12121990};
CC pH dependence:
CC Optimum pH is 8.1 with spermidine as substrate. Optimum pH is 8.5
CC with glutathionylspermidine as substrate.
CC {ECO:0000269|PubMed:12121990};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:12121990}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the
CC glutathionylspermidine synthase preATP-grasp family. {ECO:0000305}.
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; AF311782; AAL26803.1; -; Genomic_DNA.
DR EMBL; AF283000; AAG15408.1; -; Genomic_DNA.
DR EMBL; AF283001; AAG15409.1; -; Genomic_DNA.
DR EMBL; AY155571; AAO00722.1; -; Genomic_DNA.
DR EMBL; AAHK01000291; EAN94225.1; -; Genomic_DNA.
DR EMBL; AAHK01000838; EAN88749.1; -; Genomic_DNA.
DR RefSeq; XP_810600.1; XM_805507.1.
DR RefSeq; XP_816076.1; XM_810983.1.
DR AlphaFoldDB; Q9GT49; -.
DR SMR; Q9GT49; -.
DR STRING; 5693.XP_810600.1; -.
DR BindingDB; Q9GT49; -.
DR MEROPS; C51.A01; -.
DR PaxDb; Q9GT49; -.
DR PRIDE; Q9GT49; -.
DR EnsemblProtists; EAN88749; EAN88749; Tc00.1047053509319.90.
DR EnsemblProtists; EAN94225; EAN94225; Tc00.1047053509099.50.
DR GeneID; 3541408; -.
DR GeneID; 3547898; -.
DR KEGG; tcr:509099.50; -.
DR KEGG; tcr:509319.90; -.
DR eggNOG; ENOG502QUZK; Eukaryota.
DR OrthoDB; 1021702at2759; -.
DR BRENDA; 6.3.1.9; 6524.
DR Proteomes; UP000002296; Unassembled WGS sequence.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008885; F:glutathionylspermidine synthase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0047479; F:trypanothione synthase activity; IDA:UniProtKB.
DR GO; GO:0019342; P:trypanothione biosynthetic process; IDA:UniProtKB.
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 1: Evidence at protein level;
KW ATP-binding; Ligase; Magnesium; Metal-binding; Multifunctional enzyme;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..647
FT /note="Trypanothione synthetase"
FT /id="PRO_0000403111"
FT DOMAIN 26..166
FT /note="Peptidase C51"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00048"
FT BINDING 316..318
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
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 332
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
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 334
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 501
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 536
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 543
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 571
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 606..608
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT SITE 316
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT VARIANT 2
FT /note="P -> T (in strain: Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990"
FT VARIANT 5
FT /note="Q -> K (in strain: Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990"
FT VARIANT 71
FT /note="D -> E (in allele TRS-2)"
FT /evidence="ECO:0000269|PubMed:12826302"
FT VARIANT 89
FT /note="K -> Q (in allele TRS-2 and strain Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990,
FT ECO:0000269|PubMed:12826302"
FT VARIANT 90
FT /note="P -> N (in allele TRS-2)"
FT /evidence="ECO:0000269|PubMed:12826302"
FT VARIANT 106
FT /note="V -> A (in allele TRS-2)"
FT /evidence="ECO:0000269|PubMed:12826302"
FT VARIANT 132
FT /note="K -> N (in allele TRS-2)"
FT /evidence="ECO:0000269|PubMed:12826302"
FT VARIANT 175
FT /note="K -> R (in allele TRS-2)"
FT /evidence="ECO:0000269|PubMed:12826302"
FT VARIANT 184
FT /note="D -> E (in allele TRS-2 and strain Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990,
FT ECO:0000269|PubMed:12826302"
FT VARIANT 207
FT /note="L -> V (in allele TRS-2 and strain Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990,
FT ECO:0000269|PubMed:12826302"
FT VARIANT 218
FT /note="T -> N (in allele TRS-2 and strain Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990,
FT ECO:0000269|PubMed:12826302"
FT VARIANT 237
FT /note="D -> G (in strain: Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990"
FT VARIANT 237
FT /note="D -> S (in allele TRS-2)"
FT /evidence="ECO:0000269|PubMed:12826302"
FT VARIANT 248
FT /note="L -> V (in allele TRS-2 and strain Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990,
FT ECO:0000269|PubMed:12826302"
FT VARIANT 265
FT /note="A -> T (in allele TRS-2)"
FT /evidence="ECO:0000269|PubMed:12826302"
FT VARIANT 265
FT /note="A -> V (in strain: Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990"
FT VARIANT 283
FT /note="L -> I (in allele TRS-2 and strain Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990,
FT ECO:0000269|PubMed:12826302"
FT VARIANT 288
FT /note="L -> Q (in allele TRS-2 and strain Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990,
FT ECO:0000269|PubMed:12826302"
FT VARIANT 291
FT /note="L -> V (in allele TRS-2)"
FT /evidence="ECO:0000269|PubMed:12826302"
FT VARIANT 293
FT /note="C -> H (in allele TRS-2 and strain Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990,
FT ECO:0000269|PubMed:12826302"
FT VARIANT 304..305
FT /note="HS -> YL (in strain: Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990"
FT VARIANT 365
FT /note="S -> C (in allele TRS-2)"
FT /evidence="ECO:0000269|PubMed:12826302"
FT VARIANT 369
FT /note="V -> I (in allele TRS-2 and strain Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990,
FT ECO:0000269|PubMed:12826302"
FT VARIANT 381
FT /note="E -> G (in strain: Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990"
FT VARIANT 392
FT /note="N -> K (in allele TRS-2 and strain Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990,
FT ECO:0000269|PubMed:12826302"
FT VARIANT 397
FT /note="H -> Y (in allele TRS-2 and strain Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990,
FT ECO:0000269|PubMed:12826302"
FT VARIANT 487
FT /note="L -> M (in strain: Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990"
FT VARIANT 498
FT /note="P -> S (in strain: Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990"
FT VARIANT 526
FT /note="V -> I (in strain: Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990"
FT VARIANT 535
FT /note="R -> K (in allele TRS-2 and strain Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990,
FT ECO:0000269|PubMed:12826302"
FT VARIANT 562
FT /note="D -> N (in allele TRS-2 and strain Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990,
FT ECO:0000269|PubMed:12826302"
FT VARIANT 564
FT /note="S -> L (in strain: Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990"
FT VARIANT 604
FT /note="K -> T (in strain: Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990"
FT VARIANT 615
FT /note="S -> I (in allele TRS-2)"
FT /evidence="ECO:0000269|PubMed:12826302"
FT VARIANT 615
FT /note="S -> R (in strain: Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990"
FT VARIANT 624
FT /note="Q -> P (in allele TRS-2)"
FT /evidence="ECO:0000269|PubMed:12826302"
FT VARIANT 635
FT /note="K -> N (in strain: Silvio X10/7)"
FT /evidence="ECO:0000269|PubMed:12121990"
SQ SEQUENCE 647 AA; 73458 MW; CA8C76ACD0D90F24 CRC64;
MPTLQSLAVP FGCVQGYAPG GIPAYSNKHE SYFSGERSID GNLFCGFKYQ CVEFARRWLF
ERKSLVLPDV DWAVHIFNLK EVSDARTGKP VRCVAIRNGT AAKPVVDSLL IYPSDDYSPV
GHVAAITEVG DKWVRIADQN HRFHKWDANY AAELPLIHEK GVWTILDPLE DEVLKPLGWV
TFPDTPDRNP NEPLVLHESL HFKRGELPTL RRLTFTPTSR EKDWLDLTNE AEAYFADVCG
IDVKNPKLEK ASYYQMNREL YLDCAKYGNQ LHQMFLEATK FVLGSDELLR LFCIPEEYWP
RLRHSWETQP HAITGRFDFA FDEDTQQFKC FEYNADSAST LLECGVIQQK WARSVGLDDG
TTYSSGSLVS SRLQLAWEMA EVTGRVHFLI DNDDEEHYTA LYVMQHASAA GLETKLCVLF
DEFHFDENGV VVDSDGVAVT TVWKTWMWET AIADHQKARV QRGNDWRPTP KDEVRLCDIL
LGPNWDLRVF EPMWKIIPSN KAILPIIYNK HPDHPALLRA SYELTVELQR TGYVRKPIVG
RVGRNVTVTE ASGDIAAKSD GDFSDRDMVY QELFRLPERD GYYAILGGWV IGDVYCGTGV
REDKTIITGL ESPFSALRVY QGAQRRPLTH EDLDKAEAAA VGGGLKT
