TPIS_PLAFA
ID TPIS_PLAFA Reviewed; 248 AA.
AC Q07412;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Triosephosphate isomerase {ECO:0000303|PubMed:7903426};
DE Short=PfTIM {ECO:0000303|PubMed:12403619};
DE EC=5.3.1.1 {ECO:0000269|PubMed:19622869, ECO:0000269|PubMed:26762569, ECO:0000269|PubMed:7903426};
DE AltName: Full=Triose-phosphate isomerase;
GN Name=TPI {ECO:0000303|PubMed:7903426};
OS Plasmodium falciparum.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5833;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RC STRAIN=Palo Alto;
RX PubMed=7903426; DOI=10.1016/0166-6851(93)90062-3;
RA Ranie J., Kumar V.P., Balaram H.;
RT "Cloning of the triosephosphate isomerase gene of Plasmodium falciparum and
RT expression in Escherichia coli.";
RL Mol. Biochem. Parasitol. 61:159-169(1993).
RN [2] {ECO:0007744|PDB:1YDV}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), AND HOMODIMERIZATION.
RX PubMed=9261072; DOI=10.1016/s0969-2126(97)00230-x;
RA Velanker S.S., Ray S.S., Gokhale R.S., Suma S., Balaram H., Balaram P.,
RA Murthy M.R.N.;
RT "Triosephosphate isomerase from Plasmodium falciparum: the crystal
RT structure provides insights into antimalarial drug design.";
RL Structure 5:751-761(1997).
RN [3] {ECO:0007744|PDB:1M7O, ECO:0007744|PDB:1M7P}
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS,
RP AND HOMODIMERIZATION.
RX PubMed=12454456; DOI=10.1107/s0907444902015433;
RA Parthasarathy S., Balaram H., Balaram P., Murthy M.R.N.;
RT "Structures of Plasmodium falciparum triosephosphate isomerase complexed to
RT substrate analogues: observation of the catalytic loop in the open
RT conformation in the ligand-bound state.";
RL Acta Crystallogr. D 58:1992-2000(2002).
RN [4] {ECO:0007744|PDB:1LYX, ECO:0007744|PDB:1LZO}
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG, AND
RP HOMODIMERIZATION.
RX PubMed=12403619; DOI=10.1021/bi025783a;
RA Parthasarathy S., Ravindra G., Balaram H., Balaram P., Murthy M.R.N.;
RT "Structure of the Plasmodium falciparum triosephosphate isomerase-
RT phosphoglycolate complex in two crystal forms: characterization of
RT catalytic loop open and closed conformations in the ligand-bound state.";
RL Biochemistry 41:13178-13188(2002).
RN [5] {ECO:0007744|PDB:1O5X}
RP X-RAY CRYSTALLOGRAPHY (1.1 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG.
RX PubMed=14563846; DOI=10.1074/jbc.m308525200;
RA Parthasarathy S., Eaazhisai K., Balaram H., Balaram P., Murthy M.R.N.;
RT "Structure of Plasmodium falciparum triose-phosphate isomerase-2-
RT phosphoglycerate complex at 1.1-A resolution.";
RL J. Biol. Chem. 278:52461-52470(2003).
RN [6] {ECO:0007744|PDB:1VGA, ECO:0007744|PDB:1WOA, ECO:0007744|PDB:1WOB}
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG.
RX PubMed=15465054; DOI=10.1016/j.jmb.2004.08.060;
RA Eaazhisai K., Balaram H., Balaram P., Murthy M.R.N.;
RT "Structures of unliganded and inhibitor complexes of W168F, a Loop6 hinge
RT mutant of Plasmodium falciparum triosephosphate isomerase: observation of
RT an intermediate position of loop6.";
RL J. Mol. Biol. 343:671-684(2004).
RN [7] {ECO:0007744|PDB:2VFD, ECO:0007744|PDB:2VFE, ECO:0007744|PDB:2VFF, ECO:0007744|PDB:2VFG, ECO:0007744|PDB:2VFH, ECO:0007744|PDB:2VFI}
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF WILD TYPE AND MUTANTS SER-96;
RP HIS-96 AND TRP-96 IN COMPLEX WITH SUBSTRATE ANALOG, FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF PHE-96.
RX PubMed=19622869; DOI=10.1107/s0907444909018666;
RA Gayathri P., Banerjee M., Vijayalakshmi A., Balaram H., Balaram P.,
RA Murthy M.R.;
RT "Biochemical and structural characterization of residue 96 mutants of
RT Plasmodium falciparum triosephosphate isomerase: active-site loop
RT conformation, hydration and identification of a dimer-interface ligand-
RT binding site.";
RL Acta Crystallogr. D 65:847-857(2009).
RN [8] {ECO:0007744|PDB:4YWI, ECO:0007744|PDB:4YXG, ECO:0007744|PDB:4Z0J, ECO:0007744|PDB:4Z0S}
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF MUTANTS SER-96/VAL167; TYR-96;
RP SER096/ALA-73 AND ALA-96, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND MUTAGENESIS OF SER-73; PHE-96 AND LEU-167.
RX PubMed=26762569; DOI=10.1002/cbic.201500532;
RA Pareek V., Samanta M., Joshi N.V., Balaram H., Murthy M.R., Balaram P.;
RT "Connecting Active-Site Loop Conformations and Catalysis in Triosephosphate
RT Isomerase: Insights from a Rare Variation at Residue 96 in the Plasmodial
RT Enzyme.";
RL ChemBioChem 17:620-629(2016).
CC -!- FUNCTION: Catalyzes the interconversion of glyceraldehyde 3-phosphate
CC and dihydroxyacetone phosphate in the glycolytic and gluconeogenic
CC pathways. {ECO:0000269|PubMed:19622869, ECO:0000269|PubMed:26762569,
CC ECO:0000269|PubMed:7903426}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-glyceraldehyde 3-phosphate = dihydroxyacetone phosphate;
CC Xref=Rhea:RHEA:18585, ChEBI:CHEBI:57642, ChEBI:CHEBI:59776;
CC EC=5.3.1.1; Evidence={ECO:0000269|PubMed:19622869,
CC ECO:0000269|PubMed:26762569, ECO:0000269|PubMed:7903426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18586;
CC Evidence={ECO:0000269|PubMed:7903426};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.35 mM for D-glyceraldehyde-3-phosphate (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:26762569};
CC KM=0.39 mM for D-glyceraldehyde-3-phosphate (at pH 7.6)
CC {ECO:0000269|PubMed:19622869};
CC Note=kcat is 4300 sec(-1) with D-glyceraldehyde-3-phosphate as
CC substrate (at 25 degrees Celsius) (PubMed:26762569). kcat is 4233
CC sec(-1) with D-glyceraldehyde-3-phosphate as substrate (at pH 7.6)
CC (PubMed:19622869). {ECO:0000269|PubMed:19622869,
CC ECO:0000269|PubMed:26762569};
CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC {ECO:0000305|PubMed:7903426}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate from glycerone phosphate: step 1/1.
CC {ECO:0000305|PubMed:7903426}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12403619,
CC ECO:0000269|PubMed:12454456, ECO:0000269|PubMed:14563846,
CC ECO:0000269|PubMed:15465054}.
CC -!- INTERACTION:
CC Q07412; Q07412: TPI; NbExp=5; IntAct=EBI-7086711, EBI-7086711;
CC -!- SIMILARITY: Belongs to the triosephosphate isomerase family.
CC {ECO:0000305}.
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DR EMBL; L01654; AAA18799.1; -; mRNA.
DR PDB; 1LYX; X-ray; 1.90 A; A=1-248.
DR PDB; 1LZO; X-ray; 2.80 A; A/B/C/D=1-248.
DR PDB; 1M7O; X-ray; 2.40 A; A/B=1-248.
DR PDB; 1M7P; X-ray; 2.40 A; A/B=1-248.
DR PDB; 1O5X; X-ray; 1.10 A; A/B=1-248.
DR PDB; 1VGA; X-ray; 1.80 A; A/B/C/D=1-248.
DR PDB; 1WOA; X-ray; 2.80 A; A/B/C/D=1-248.
DR PDB; 1WOB; X-ray; 2.80 A; A/B/C/D=1-248.
DR PDB; 1YDV; X-ray; 2.20 A; A/B=1-248.
DR PDB; 2VFD; X-ray; 1.40 A; A/B=1-248.
DR PDB; 2VFE; X-ray; 2.20 A; A/B=1-248.
DR PDB; 2VFF; X-ray; 1.70 A; A/B=1-248.
DR PDB; 2VFG; X-ray; 1.95 A; A/B/C/D=1-248.
DR PDB; 2VFH; X-ray; 2.00 A; A/B=1-248.
DR PDB; 2VFI; X-ray; 2.25 A; A/B=1-248.
DR PDB; 3PSV; X-ray; 2.00 A; A/B=1-248.
DR PDB; 3PSW; X-ray; 1.99 A; A/B=1-248.
DR PDB; 3PVF; X-ray; 1.73 A; A=1-248.
DR PDB; 3PWA; X-ray; 2.04 A; A/B=1-248.
DR PDB; 3PY2; X-ray; 1.93 A; A/B=1-248.
DR PDB; 4YWI; X-ray; 1.85 A; A/B=1-248.
DR PDB; 4YXG; X-ray; 1.90 A; A/B=1-248.
DR PDB; 4Z0J; X-ray; 2.07 A; A/B=1-248.
DR PDB; 4Z0S; X-ray; 2.39 A; A/B=1-248.
DR PDB; 4ZZ9; X-ray; 1.81 A; A/B=1-248.
DR PDB; 5BMW; X-ray; 1.86 A; A/B=1-248.
DR PDB; 5BMX; X-ray; 1.80 A; A/B/C/D=1-248.
DR PDB; 5BNK; X-ray; 1.80 A; A/B=1-248.
DR PDB; 5BRB; X-ray; 2.53 A; A/B=1-248.
DR PDB; 5GV4; X-ray; 2.09 A; A=1-248.
DR PDB; 5GZP; X-ray; 2.03 A; A/B=1-248.
DR PDBsum; 1LYX; -.
DR PDBsum; 1LZO; -.
DR PDBsum; 1M7O; -.
DR PDBsum; 1M7P; -.
DR PDBsum; 1O5X; -.
DR PDBsum; 1VGA; -.
DR PDBsum; 1WOA; -.
DR PDBsum; 1WOB; -.
DR PDBsum; 1YDV; -.
DR PDBsum; 2VFD; -.
DR PDBsum; 2VFE; -.
DR PDBsum; 2VFF; -.
DR PDBsum; 2VFG; -.
DR PDBsum; 2VFH; -.
DR PDBsum; 2VFI; -.
DR PDBsum; 3PSV; -.
DR PDBsum; 3PSW; -.
DR PDBsum; 3PVF; -.
DR PDBsum; 3PWA; -.
DR PDBsum; 3PY2; -.
DR PDBsum; 4YWI; -.
DR PDBsum; 4YXG; -.
DR PDBsum; 4Z0J; -.
DR PDBsum; 4Z0S; -.
DR PDBsum; 4ZZ9; -.
DR PDBsum; 5BMW; -.
DR PDBsum; 5BMX; -.
DR PDBsum; 5BNK; -.
DR PDBsum; 5BRB; -.
DR PDBsum; 5GV4; -.
DR PDBsum; 5GZP; -.
DR AlphaFoldDB; Q07412; -.
DR SMR; Q07412; -.
DR MINT; Q07412; -.
DR DrugBank; DB01709; 2-phospho-D-glyceric acid.
DR DrugBank; DB02726; 2-Phosphoglycolic Acid.
DR DrugBank; DB02951; 3-Hydroxypyruvic Acid.
DR DrugBank; DB04510; 3-phospho-D-glyceric acid.
DR DrugBank; DB01779; Glycerol 2-phosphate.
DR DrugBank; DB02515; sn-glycerol 3-phosphate.
DR EnsemblProtists; CZU00095; CZU00095; PF3D7_1439900.
DR VEuPathDB; PlasmoDB:PF3D7_1439900; -.
DR VEuPathDB; PlasmoDB:Pf7G8-2_000513700; -.
DR VEuPathDB; PlasmoDB:Pf7G8_140045200; -.
DR VEuPathDB; PlasmoDB:PfCD01_140045400; -.
DR VEuPathDB; PlasmoDB:PfDd2_140044400; -.
DR VEuPathDB; PlasmoDB:PfGA01_140045500; -.
DR VEuPathDB; PlasmoDB:PfGB4_140046100; -.
DR VEuPathDB; PlasmoDB:PfGN01_140045300; -.
DR VEuPathDB; PlasmoDB:PfHB3_140045700; -.
DR VEuPathDB; PlasmoDB:PfIT_140046400; -.
DR VEuPathDB; PlasmoDB:PfKE01_140044900; -.
DR VEuPathDB; PlasmoDB:PfKH01_140045500; -.
DR VEuPathDB; PlasmoDB:PfKH02_140045700; -.
DR VEuPathDB; PlasmoDB:PfML01_140045500; -.
DR VEuPathDB; PlasmoDB:PfNF135_140044100; -.
DR VEuPathDB; PlasmoDB:PfNF166_140042800; -.
DR VEuPathDB; PlasmoDB:PfNF54_140043700; -.
DR VEuPathDB; PlasmoDB:PfSD01_140043300; -.
DR VEuPathDB; PlasmoDB:PfSN01_140047200; -.
DR VEuPathDB; PlasmoDB:PfTG01_140045300; -.
DR OMA; QEVCGAI; -.
DR BRENDA; 5.3.1.1; 4889.
DR SABIO-RK; Q07412; -.
DR UniPathway; UPA00109; UER00189.
DR UniPathway; UPA00138; -.
DR EvolutionaryTrace; Q07412; -.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004807; F:triose-phosphate isomerase activity; IDA:CACAO.
DR GO; GO:0006094; P:gluconeogenesis; IEA:UniProtKB-UniPathway.
DR GO; GO:0006096; P:glycolytic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00311; TIM; 1.
DR DisProt; DP00614; -.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_00147_B; TIM_B; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR035990; TIM_sf.
DR InterPro; IPR022896; TrioseP_Isoase_bac/euk.
DR InterPro; IPR000652; Triosephosphate_isomerase.
DR InterPro; IPR020861; Triosephosphate_isomerase_AS.
DR PANTHER; PTHR21139; PTHR21139; 1.
DR Pfam; PF00121; TIM; 1.
DR SUPFAM; SSF51351; SSF51351; 1.
DR TIGRFAMs; TIGR00419; tim; 1.
DR PROSITE; PS00171; TIM_1; 1.
DR PROSITE; PS51440; TIM_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Gluconeogenesis; Glycolysis; Isomerase.
FT CHAIN 1..248
FT /note="Triosephosphate isomerase"
FT /id="PRO_0000090138"
FT ACT_SITE 95
FT /note="Electrophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10127"
FT ACT_SITE 165
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10127"
FT BINDING 10
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000269|PubMed:12454456,
FT ECO:0000269|PubMed:14563846, ECO:0000269|PubMed:19622869,
FT ECO:0007744|PDB:1M7O, ECO:0007744|PDB:1O5X,
FT ECO:0007744|PDB:2VFI"
FT BINDING 12
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000269|PubMed:12403619,
FT ECO:0000269|PubMed:15465054, ECO:0000269|PubMed:19622869,
FT ECO:0007744|PDB:1LYX, ECO:0007744|PDB:1LZO,
FT ECO:0007744|PDB:1WOA, ECO:0007744|PDB:2VFI"
FT BINDING 171
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000269|PubMed:12403619,
FT ECO:0000269|PubMed:19622869, ECO:0007744|PDB:1LYX,
FT ECO:0007744|PDB:2VFI"
FT BINDING 230
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000269|PubMed:12454456,
FT ECO:0000269|PubMed:14563846, ECO:0000269|PubMed:15465054,
FT ECO:0000269|PubMed:19622869, ECO:0007744|PDB:1M7O,
FT ECO:0007744|PDB:1O5X, ECO:0007744|PDB:1WOA,
FT ECO:0007744|PDB:2VFI"
FT BINDING 232..233
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000269|PubMed:12403619,
FT ECO:0000269|PubMed:12454456, ECO:0000269|PubMed:14563846,
FT ECO:0000269|PubMed:15465054, ECO:0000269|PubMed:19622869,
FT ECO:0000312|PDB:1LZO, ECO:0007744|PDB:1LYX,
FT ECO:0007744|PDB:1M7O, ECO:0007744|PDB:1M7P,
FT ECO:0007744|PDB:1O5X, ECO:0007744|PDB:1WOA,
FT ECO:0007744|PDB:2VFI"
FT MUTAGEN 73
FT /note="S->A: 3-fold decrease in substrate affinity; when
FT associated with S-96."
FT /evidence="ECO:0000269|PubMed:26762569"
FT MUTAGEN 96
FT /note="F->A: 2-fold decrease in substrate affinity."
FT /evidence="ECO:0000269|PubMed:26762569"
FT MUTAGEN 96
FT /note="F->H: 6.7-fold decrease in substrate affinity."
FT /evidence="ECO:0000269|PubMed:19622869"
FT MUTAGEN 96
FT /note="F->S: 5.5-fold decrease in substrate affinity. 3-
FT fold decrease in substrate affinity; when associated with
FT A-73 or V-167."
FT /evidence="ECO:0000269|PubMed:19622869,
FT ECO:0000269|PubMed:26762569"
FT MUTAGEN 96
FT /note="F->W: 3-fold decrease in substrate affinity."
FT /evidence="ECO:0000269|PubMed:19622869"
FT MUTAGEN 96
FT /note="F->Y: 5-fold decrease in substrate affinity."
FT /evidence="ECO:0000269|PubMed:26762569"
FT MUTAGEN 167
FT /note="L->V: 3-fold decrease in substrate affinity; when
FT associated with S-96."
FT /evidence="ECO:0000269|PubMed:26762569"
FT STRAND 5..10
FT /evidence="ECO:0007829|PDB:1O5X"
FT HELIX 17..28
FT /evidence="ECO:0007829|PDB:1O5X"
FT TURN 34..36
FT /evidence="ECO:0007829|PDB:1O5X"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:1O5X"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:1O5X"
FT HELIX 48..54
FT /evidence="ECO:0007829|PDB:1O5X"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:1O5X"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:1O5X"
FT HELIX 80..85
FT /evidence="ECO:0007829|PDB:1O5X"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:1O5X"
FT HELIX 96..101
FT /evidence="ECO:0007829|PDB:1O5X"
FT HELIX 106..118
FT /evidence="ECO:0007829|PDB:1O5X"
FT STRAND 122..127
FT /evidence="ECO:0007829|PDB:1O5X"
FT HELIX 131..135
FT /evidence="ECO:0007829|PDB:1O5X"
FT HELIX 139..148
FT /evidence="ECO:0007829|PDB:1O5X"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:1O5X"
FT STRAND 159..164
FT /evidence="ECO:0007829|PDB:1O5X"
FT HELIX 167..169
FT /evidence="ECO:0007829|PDB:1O5X"
FT STRAND 170..173
FT /evidence="ECO:0007829|PDB:1O5X"
FT HELIX 178..195
FT /evidence="ECO:0007829|PDB:1O5X"
FT HELIX 198..203
FT /evidence="ECO:0007829|PDB:1O5X"
FT STRAND 204..208
FT /evidence="ECO:0007829|PDB:1O5X"
FT TURN 214..216
FT /evidence="ECO:0007829|PDB:1O5X"
FT HELIX 217..221
FT /evidence="ECO:0007829|PDB:1O5X"
FT STRAND 228..231
FT /evidence="ECO:0007829|PDB:1O5X"
FT HELIX 233..236
FT /evidence="ECO:0007829|PDB:1O5X"
FT HELIX 240..246
FT /evidence="ECO:0007829|PDB:1O5X"
SQ SEQUENCE 248 AA; 27935 MW; EFC8A4373EA9BED1 CRC64;
MARKYFVAAN WKCNGTLESI KSLTNSFNNL DFDPSKLDVV VFPVSVHYDH TRKLLQSKFS
TGIQNVSKFG NGSYTGEVSA EIAKDLNIEY VIIGHFERRK YFHETDEDVR EKLQASLKNN
LKAVVCFGES LEQREQNKTI EVITKQVKAF VDLIDNFDNV ILAYEPLWAI GTGKTATPEQ
AQLVHKEIRK IVKDTCGEKQ ANQIRILYGG SVNTENCSSL IQQEDIDGFL VGNASLKESF
VDIIKSAM
