SYP_PLAF7
ID SYP_PLAF7 Reviewed; 746 AA.
AC Q8I5R7; A0A144A0G8;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Proline--tRNA ligase;
DE Short=PfPRS {ECO:0000303|PubMed:25817387};
DE EC=6.1.1.15 {ECO:0000269|PubMed:25817387, ECO:0000269|PubMed:27798837};
DE AltName: Full=Prolyl-tRNA synthetase {ECO:0000303|PubMed:14663147};
DE Short=PfProRS {ECO:0000303|PubMed:14663147};
GN Name=proRS {ECO:0000303|PubMed:14663147};
GN Synonyms=PRS {ECO:0000303|PubMed:25817387};
GN ORFNames=PF3D7_1213800, PFL0670c;
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [2]
RP FUNCTION AS TRNA(PRO) EDITING PROTEIN.
RX PubMed=14663147; DOI=10.1073/pnas.2136934100;
RA Ahel I., Korencic D., Ibba M., Soll D.;
RT "Trans-editing of mischarged tRNAs.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:15422-15427(2003).
RN [3] {ECO:0007744|PDB:4TWA}
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 254-746, SUBUNIT, SUBCELLULAR
RP LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=25047712; DOI=10.1007/s10969-014-9186-x;
RA Jain V., Kikuchi H., Oshima Y., Sharma A., Yogavel M.;
RT "Structural and functional analysis of the anti-malarial drug target
RT prolyl-tRNA synthetase.";
RL J. Struct. Funct. Genomics 15:181-190(2014).
RN [4] {ECO:0007744|PDB:4OLF}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 249-746 IN COMPLEX WITH ATP
RP ANALOG.
RA Dranow D.M., Edwards T.E., Lorimer D.;
RT "Crystal Structure of Prolyl-tRNA synthetase (ProRS, Proline--tRNA
RT ligase)from Plasmodium falciparum in complex with Halofuginone and
RT AMPPNP.";
RL Submitted (JAN-2014) to the PDB data bank.
RN [5] {ECO:0007744|PDB:4YDQ}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 254-746 IN COMPLEX WITH ATP
RP ANALOG AND INHIBITOR, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP AND SUBUNIT.
RX PubMed=25817387; DOI=10.1016/j.str.2015.02.011;
RA Jain V., Yogavel M., Oshima Y., Kikuchi H., Touquet B., Hakimi M.A.,
RA Sharma A.;
RT "Structure of Prolyl-tRNA Synthetase-Halofuginone Complex Provides Basis
RT for Development of Drugs against Malaria and Toxoplasmosis.";
RL Structure 23:819-829(2015).
RN [6] {ECO:0007744|PDB:4NCX, ECO:0007744|PDB:4Q15, ECO:0007744|PDB:4WI1, ECO:0007744|PDB:5IFU}
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 249-746 IN APO FORM AND IN
RP COMPLEX WITH ATP ANALOG AND INHIBITOR, FUNCTION, CATALYTIC ACTIVITY, AND
RP ACTIVITY REGULATION.
RX PubMed=27798837; DOI=10.1021/acsinfecdis.6b00078;
RA Hewitt S.N., Dranow D.M., Horst B.G., Abendroth J.A., Forte B.,
RA Hallyburton I., Jansen C., Baragana B., Choi R., Rivas K.L.,
RA Hulverson M.A., Dumais M., Edwards T.E., Lorimer D.D., Fairlamb A.H.,
RA Gray D.W., Read K.D., Lehane A.M., Kirk K., Myler P.J., Wernimont A.,
RA Walpole C., Stacy R., Barrett L.K., Gilbert I.H., Van Voorhis W.C.;
RT "Biochemical and Structural Characterization of Selective Allosteric
RT Inhibitors of the Plasmodium falciparum Drug Target, Prolyl-tRNA-
RT synthetase.";
RL ACS Infect. Dis. 3:34-44(2017).
RN [7] {ECO:0007744|PDB:6T7K}
RP X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 249-746 IN COMPLEX WITH
RP L-PROLINE.
RA Johansson C., Wang J., Tye M., Payne N.C., Mazitschek R., Thompson A.,
RA Arrowsmith C.H., Bountra C., Edwards A., Oppermann U.C.T.;
RT "Crystal Structure of Prolyl-tRNA synthetase (ProRS, Proline--tRNA ligase)
RT from Plasmodium falciparum in complex with NCP-26 and L-Proline.";
RL Submitted (OCT-2019) to the PDB data bank.
CC -!- FUNCTION: Catalyzes the attachment of proline to tRNA(Pro) in a two-
CC step reaction: proline is first activated by ATP to form Pro-AMP and
CC then transferred to the acceptor end of tRNA(Pro) (PubMed:25817387,
CC PubMed:27798837). Functions in trans to edit the amino acid moiety from
CC incorrectly charged Ala-tRNA(Pro) (PubMed:14663147). Has no activity on
CC correctly charged Pro-tRNA(Pro) or Ala-tRNA(Ala) (PubMed:14663147).
CC {ECO:0000269|PubMed:14663147, ECO:0000269|PubMed:25817387,
CC ECO:0000269|PubMed:27798837}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-proline + tRNA(Pro) = AMP + diphosphate + L-prolyl-
CC tRNA(Pro); Xref=Rhea:RHEA:14305, Rhea:RHEA-COMP:9700, Rhea:RHEA-
CC COMP:9702, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:60039,
CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78532, ChEBI:CHEBI:456215;
CC EC=6.1.1.15; Evidence={ECO:0000269|PubMed:25817387,
CC ECO:0000269|PubMed:27798837};
CC -!- ACTIVITY REGULATION: Inhibited by the quinazolinone-based compound
CC febrifugine from the Chinese plant Dichroa febrifuga which is used to
CC treat malaria-associated fever (PubMed:25817387, PubMed:27798837). Also
CC inhibited by febrifugine derivatives such as halofuginone
CC (PubMed:25817387, PubMed:27798837). {ECO:0000269|PubMed:25817387,
CC ECO:0000269|PubMed:27798837}.
CC -!- SUBUNIT: Homodimer. {ECO:0000305|PubMed:25047712,
CC ECO:0000305|PubMed:25817387}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25047712}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the asexual blood stage including
CC at the ring stage and in trophozoites and schizonts (at protein level).
CC {ECO:0000269|PubMed:25047712}.
CC -!- DOMAIN: Consists of four domains: the N-terminal editing domain, the N-
CC terminal catalytic domain, the anticodon-binding domain and the C-
CC terminal extension (Probable). The first domain (about residues 1-163)
CC is required for editing of incorrectly charged tRNA (PubMed:14663147).
CC When it is deleted the enzyme shows pronounced misacylation of
CC tRNA(Pro) with alanine (PubMed:14663147). {ECO:0000269|PubMed:14663147,
CC ECO:0000305|PubMed:14663147}.
CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC ProS type 3 subfamily. {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; LN999947; CZT99299.1; -; Genomic_DNA.
DR RefSeq; XP_001350543.1; XM_001350507.1.
DR PDB; 4NCX; X-ray; 1.85 A; A/B=249-746.
DR PDB; 4OLF; X-ray; 2.90 A; A=249-746.
DR PDB; 4Q15; X-ray; 2.35 A; A/B=249-746.
DR PDB; 4TWA; X-ray; 3.00 A; A/B=254-746.
DR PDB; 4WI1; X-ray; 1.65 A; A/B=249-746.
DR PDB; 4YDQ; X-ray; 2.30 A; A/B=254-746.
DR PDB; 5IFU; X-ray; 2.45 A; A/B=249-746.
DR PDB; 6T7K; X-ray; 1.79 A; A=249-746.
DR PDB; 7QB7; X-ray; 1.90 A; A=249-746.
DR PDB; 7QC1; X-ray; 2.51 A; A/D/I=249-746.
DR PDBsum; 4NCX; -.
DR PDBsum; 4OLF; -.
DR PDBsum; 4Q15; -.
DR PDBsum; 4TWA; -.
DR PDBsum; 4WI1; -.
DR PDBsum; 4YDQ; -.
DR PDBsum; 5IFU; -.
DR PDBsum; 6T7K; -.
DR PDBsum; 7QB7; -.
DR PDBsum; 7QC1; -.
DR AlphaFoldDB; Q8I5R7; -.
DR SMR; Q8I5R7; -.
DR DIP; DIP-61496N; -.
DR STRING; 5833.PFL0670c; -.
DR ChEMBL; CHEMBL3301560; -.
DR GuidetoPHARMACOLOGY; 3056; -.
DR PRIDE; Q8I5R7; -.
DR EnsemblProtists; CZT99299; CZT99299; PF3D7_1213800.
DR GeneID; 811187; -.
DR KEGG; pfa:PF3D7_1213800; -.
DR VEuPathDB; PlasmoDB:PF3D7_1213800; -.
DR HOGENOM; CLU_001882_4_1_1; -.
DR InParanoid; Q8I5R7; -.
DR OMA; EVYWVTH; -.
DR PhylomeDB; Q8I5R7; -.
DR BRENDA; 6.1.1.15; 4889.
DR Proteomes; UP000001450; Chromosome 12.
DR GO; GO:0017101; C:aminoacyl-tRNA synthetase multienzyme complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:GeneDB.
DR GO; GO:0043906; F:Ala-tRNA(Pro) hydrolase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004827; F:proline-tRNA ligase activity; ISS:GeneDB.
DR GO; GO:0006433; P:prolyl-tRNA aminoacylation; IBA:GO_Central.
DR GO; GO:0006418; P:tRNA aminoacylation for protein translation; ISS:GeneDB.
DR CDD; cd00778; ProRS_core_arch_euk; 1.
DR Gene3D; 3.30.110.30; -; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR Gene3D; 3.40.50.800; -; 1.
DR Gene3D; 3.90.960.10; -; 1.
DR HAMAP; MF_01571; Pro_tRNA_synth_type3; 1.
DR InterPro; IPR002314; aa-tRNA-synt_IIb.
DR InterPro; IPR006195; aa-tRNA-synth_II.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR004154; Anticodon-bd.
DR InterPro; IPR036621; Anticodon-bd_dom_sf.
DR InterPro; IPR002316; Pro-tRNA-ligase_IIa.
DR InterPro; IPR004499; Pro-tRNA-ligase_IIa_arc-type.
DR InterPro; IPR016061; Pro-tRNA_ligase_II_C.
DR InterPro; IPR017449; Pro-tRNA_synth_II.
DR InterPro; IPR033721; ProRS_core_arch_euk.
DR InterPro; IPR036754; YbaK/aa-tRNA-synt-asso_dom_sf.
DR InterPro; IPR007214; YbaK/aa-tRNA-synth-assoc-dom.
DR PANTHER; PTHR43382; PTHR43382; 1.
DR Pfam; PF03129; HGTP_anticodon; 1.
DR Pfam; PF09180; ProRS-C_1; 1.
DR Pfam; PF00587; tRNA-synt_2b; 1.
DR Pfam; PF04073; tRNA_edit; 1.
DR PRINTS; PR01046; TRNASYNTHPRO.
DR SMART; SM00946; ProRS-C_1; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR SUPFAM; SSF55826; SSF55826; 1.
DR SUPFAM; SSF64586; SSF64586; 1.
DR TIGRFAMs; TIGR00408; proS_fam_I; 1.
DR PROSITE; PS50862; AA_TRNA_LIGASE_II; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm; Ligase;
KW Nucleotide-binding; Protein biosynthesis; Reference proteome.
FT CHAIN 1..746
FT /note="Proline--tRNA ligase"
FT /id="PRO_0000392534"
FT REGION 1..223
FT /note="Required for editing of incorrectly charged tRNA"
FT /evidence="ECO:0000269|PubMed:14663147"
FT REGION 181..226
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 181..198
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 199..226
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 390..394
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:25817387,
FT ECO:0000269|PubMed:27798837, ECO:0000269|Ref.4,
FT ECO:0007744|PDB:4OLF, ECO:0007744|PDB:4Q15,
FT ECO:0007744|PDB:4YDQ"
FT BINDING 390
FT /ligand="L-proline"
FT /ligand_id="ChEBI:CHEBI:60039"
FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PDB:6T7K"
FT BINDING 401..405
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:25817387,
FT ECO:0000269|PubMed:27798837, ECO:0000269|Ref.4,
FT ECO:0007744|PDB:4OLF, ECO:0007744|PDB:4Q15,
FT ECO:0007744|PDB:4YDQ"
FT BINDING 475..477
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:25817387,
FT ECO:0000269|PubMed:27798837, ECO:0000269|Ref.4,
FT ECO:0007744|PDB:4OLF, ECO:0007744|PDB:4Q15,
FT ECO:0007744|PDB:4YDQ"
FT BINDING 480
FT /ligand="L-proline"
FT /ligand_id="ChEBI:CHEBI:60039"
FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PDB:6T7K"
FT BINDING 512..514
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:25817387,
FT ECO:0000269|PubMed:27798837, ECO:0000269|Ref.4,
FT ECO:0007744|PDB:4OLF, ECO:0007744|PDB:4Q15,
FT ECO:0007744|PDB:4YDQ"
FT HELIX 250..252
FT /evidence="ECO:0007829|PDB:4WI1"
FT TURN 258..260
FT /evidence="ECO:0007829|PDB:4WI1"
FT HELIX 262..272
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 275..278
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 285..287
FT /evidence="ECO:0007829|PDB:4WI1"
FT HELIX 289..308
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 312..315
FT /evidence="ECO:0007829|PDB:4Q15"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:4WI1"
FT HELIX 322..325
FT /evidence="ECO:0007829|PDB:6T7K"
FT HELIX 329..335
FT /evidence="ECO:0007829|PDB:6T7K"
FT HELIX 336..338
FT /evidence="ECO:0007829|PDB:6T7K"
FT STRAND 341..345
FT /evidence="ECO:0007829|PDB:6T7K"
FT STRAND 348..356
FT /evidence="ECO:0007829|PDB:6T7K"
FT STRAND 358..360
FT /evidence="ECO:0007829|PDB:6T7K"
FT STRAND 361..363
FT /evidence="ECO:0007829|PDB:4WI1"
FT HELIX 365..370
FT /evidence="ECO:0007829|PDB:4WI1"
FT HELIX 375..377
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 380..387
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 390..392
FT /evidence="ECO:0007829|PDB:4WI1"
FT TURN 398..400
FT /evidence="ECO:0007829|PDB:6T7K"
FT STRAND 406..416
FT /evidence="ECO:0007829|PDB:4WI1"
FT HELIX 417..437
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 444..447
FT /evidence="ECO:0007829|PDB:4WI1"
FT TURN 450..452
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 458..467
FT /evidence="ECO:0007829|PDB:4WI1"
FT TURN 468..471
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 472..483
FT /evidence="ECO:0007829|PDB:4WI1"
FT HELIX 485..490
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 493..495
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 501..503
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 505..512
FT /evidence="ECO:0007829|PDB:4WI1"
FT HELIX 514..523
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 528..530
FT /evidence="ECO:0007829|PDB:6T7K"
FT HELIX 533..535
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 539..544
FT /evidence="ECO:0007829|PDB:4WI1"
FT HELIX 549..568
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 573..575
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 579..581
FT /evidence="ECO:0007829|PDB:4TWA"
FT HELIX 583..592
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 596..601
FT /evidence="ECO:0007829|PDB:4WI1"
FT HELIX 603..608
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 610..615
FT /evidence="ECO:0007829|PDB:4WI1"
FT TURN 616..618
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 621..625
FT /evidence="ECO:0007829|PDB:4WI1"
FT HELIX 626..628
FT /evidence="ECO:0007829|PDB:4WI1"
FT HELIX 629..654
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 656..658
FT /evidence="ECO:0007829|PDB:4WI1"
FT HELIX 662..664
FT /evidence="ECO:0007829|PDB:4WI1"
FT HELIX 665..670
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 674..679
FT /evidence="ECO:0007829|PDB:4WI1"
FT HELIX 684..695
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 705..707
FT /evidence="ECO:0007829|PDB:6T7K"
FT STRAND 712..719
FT /evidence="ECO:0007829|PDB:4WI1"
FT TURN 730..732
FT /evidence="ECO:0007829|PDB:4WI1"
FT STRAND 733..735
FT /evidence="ECO:0007829|PDB:5IFU"
FT STRAND 738..743
FT /evidence="ECO:0007829|PDB:4WI1"
SQ SEQUENCE 746 AA; 86647 MW; 910F249C268E48DA CRC64;
MNNNTNGEII IPQEYLEKSE CLFKELKELN INFKEVKHGL AATIKDLLEM NLENSTNILK
NLFLKDKKKN YFLICTLNNK TVDLKNLSNI LKTNNLRFVD ENNLNNILNI QPGCLSPLAI
KNDKENIVKL YFDEEIKNMQ EVIIHPLHNY SSLYIKTQDV IKFCESFNHA PEYVQIKEDT
TSKARVDKKE DVQEEMAKNE ELQNNNNNNK NNSNSNNNNN NNNNHIKDTI LKGKLLSNNE
VEDNKSKDSN ILGITSKKIE NFSDWYTQVI VKSELIEYYD ISGCYILRPA AYYIWECVQA
FFNKEIKKLN VENSYFPLFV TKNKLEKEKN HIEGFSPEVA WVTKYGDSNL PEEIAIRPTS
ETIMYSVFPK WIRSYRDLPL KLNQWNTVVR WEFKQPTPFI RTREFLWQEG HTAHKNEEEA
VKLVFDILDL YRRWYEEYLA VPIIKGIKSE GEKFGGANFT STAEAFISEN GRAIQAATSH
YLGTNFAKMF KIEFEDENEV KQYVHQTSWG CTTRSIGIMI MTHGDDKGLV LPPNVSKYKV
VIVPIFYKTT DENAIHSYCK DIEKILKNAQ INCVYDDRAS YSPGYKFNHW ELRGIPIRIE
VGPKDLQNNS CVIVRRDNNE KCNVKKESVL LETQQMLVDI HKNLFLKAKK KLDDSIVQVT
SFSEVMNALN KKKMVLAPWC EDIATEEEIK KETQRLSLNQ TNSETTLSGA MKPLCIPLDQ
PPMPPNMKCF WSGKPAKRWC LFGRSY
