SYFA_PLAVS
ID SYFA_PLAVS Reviewed; 569 AA.
AC A5K9S0;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Phenylalanine--tRNA ligase alpha subunit {ECO:0000305};
DE EC=6.1.1.20 {ECO:0000269|PubMed:33436639};
DE AltName: Full=Phenylalanine tRNA-synthetase alpha subunit {ECO:0000303|PubMed:33436639};
DE Short=FRS {ECO:0000303|PubMed:33436639};
DE Short=PheRS {ECO:0000303|PubMed:33436639};
DE AltName: Full=Phenylalanyl-tRNA synthetase alpha subunit {ECO:0000305};
GN ORFNames=PVX_081300 {ECO:0000312|EMBL:EDL43808.1};
OS Plasmodium vivax (strain Salvador I).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX NCBI_TaxID=126793 {ECO:0000312|Proteomes:UP000008333};
RN [1] {ECO:0000312|EMBL:EDL43808.1, ECO:0000312|Proteomes:UP000008333}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Salvador I {ECO:0000312|EMBL:EDL43808.1,
RC ECO:0000312|Proteomes:UP000008333};
RX PubMed=18843361; DOI=10.1038/nature07327;
RA Carlton J.M., Adams J.H., Silva J.C., Bidwell S.L., Lorenzi H., Caler E.,
RA Crabtree J., Angiuoli S.V., Merino E.F., Amedeo P., Cheng Q.,
RA Coulson R.M.R., Crabb B.S., del Portillo H.A., Essien K., Feldblyum T.V.,
RA Fernandez-Becerra C., Gilson P.R., Gueye A.H., Guo X., Kang'a S.,
RA Kooij T.W.A., Korsinczky M., Meyer E.V.-S., Nene V., Paulsen I., White O.,
RA Ralph S.A., Ren Q., Sargeant T.J., Salzberg S.L., Stoeckert C.J.,
RA Sullivan S.A., Yamamoto M.M., Hoffman S.L., Wortman J.R., Gardner M.J.,
RA Galinski M.R., Barnwell J.W., Fraser-Liggett C.M.;
RT "Comparative genomics of the neglected human malaria parasite Plasmodium
RT vivax.";
RL Nature 455:757-763(2008).
RN [2] {ECO:0007744|PDB:7BY6}
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 271-569 IN COMPLEX WITH BETA
RP SUBUNIT; BICYCLIC AZETIDINE BRD1389 INHIBITOR AND MAGNESIUM, CATALYTIC
RP ACTIVITY, COFACTOR, ACTIVITY REGULATION, SUBUNIT, AND BIOTECHNOLOGY.
RX PubMed=33436639; DOI=10.1038/s41467-020-20478-5;
RA Sharma M., Malhotra N., Yogavel M., Harlos K., Melillo B., Comer E.,
RA Gonse A., Parvez S., Mitasev B., Fang F.G., Schreiber S.L., Sharma A.;
RT "Structural basis of malaria parasite phenylalanine tRNA-synthetase
RT inhibition by bicyclic azetidines.";
RL Nat. Commun. 12:343-343(2021).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-phenylalanine + tRNA(Phe) = AMP + diphosphate + H(+) +
CC L-phenylalanyl-tRNA(Phe); Xref=Rhea:RHEA:19413, Rhea:RHEA-COMP:9668,
CC Rhea:RHEA-COMP:9699, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:58095, ChEBI:CHEBI:78442,
CC ChEBI:CHEBI:78531, ChEBI:CHEBI:456215; EC=6.1.1.20;
CC Evidence={ECO:0000269|PubMed:33436639};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:33436639};
CC -!- ACTIVITY REGULATION: Inhibited by bicyclic azetidine BRD1389, which
CC competes for L-phenylalanine. {ECO:0000269|PubMed:33436639}.
CC -!- SUBUNIT: Heterotetramer; dimer of two heterodimers formed by alpha and
CC beta subunits. {ECO:0000269|PubMed:33436639}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q505J8}.
CC -!- BIOTECHNOLOGY: The identification of residues that recognize the
CC inhibitor lays a foundation for the development of drugs against
CC Plasmodium species as well as related apicomplexan parasites that
CC infect humans since they are conserved among apicomplexan alpha
CC subunits. {ECO:0000269|PubMed:33436639}.
CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC Phe-tRNA synthetase alpha subunit type 2 subfamily. {ECO:0000305}.
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DR EMBL; AAKM01000013; EDL43808.1; -; Genomic_DNA.
DR RefSeq; XP_001613535.1; XM_001613485.1.
DR PDB; 7BY6; X-ray; 3.00 A; A=271-569.
DR PDBsum; 7BY6; -.
DR SMR; A5K9S0; -.
DR STRING; 126793.A5K9S0; -.
DR EnsemblProtists; EDL43808; EDL43808; PVX_081300.
DR GeneID; 5472805; -.
DR KEGG; pvx:PVX_081300; -.
DR VEuPathDB; PlasmoDB:PVX_081300; -.
DR InParanoid; A5K9S0; -.
DR OMA; QIEGWVM; -.
DR PhylomeDB; A5K9S0; -.
DR Proteomes; UP000008333; Chromosome 2.
DR Proteomes; UP000008333; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0009328; C:phenylalanine-tRNA ligase complex; IC:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0004826; F:phenylalanine-tRNA ligase activity; IDA:UniProtKB.
DR GO; GO:0000049; F:tRNA binding; IEA:InterPro.
DR GO; GO:0006432; P:phenylalanyl-tRNA aminoacylation; IDA:UniProtKB.
DR GO; GO:0051290; P:protein heterotetramerization; IDA:UniProtKB.
DR Gene3D; 3.30.930.10; -; 1.
DR InterPro; IPR006195; aa-tRNA-synth_II.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR004529; Phe-tRNA-synth_IIc_asu.
DR InterPro; IPR002319; Phenylalanyl-tRNA_Synthase.
DR Pfam; PF01409; tRNA-synt_2d; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR TIGRFAMs; TIGR00468; pheS; 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 Magnesium; Metal-binding; Nucleotide-binding; Protein biosynthesis;
KW Reference proteome.
FT CHAIN 1..569
FT /note="Phenylalanine--tRNA ligase alpha subunit"
FT /id="PRO_0000456101"
FT BINDING 410
FT /ligand="L-phenylalanine"
FT /ligand_id="ChEBI:CHEBI:58095"
FT /evidence="ECO:0000250|UniProtKB:Q9Y285"
FT BINDING 457..459
FT /ligand="L-phenylalanine"
FT /ligand_id="ChEBI:CHEBI:58095"
FT /evidence="ECO:0000250|UniProtKB:Q9Y285"
FT BINDING 497
FT /ligand="L-phenylalanine"
FT /ligand_id="ChEBI:CHEBI:58095"
FT /evidence="ECO:0000250|UniProtKB:Q9Y285"
FT BINDING 499
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="shared with beta subunit"
FT /evidence="ECO:0000269|PubMed:33436639,
FT ECO:0007744|PDB:7BY6"
FT BINDING 523
FT /ligand="L-phenylalanine"
FT /ligand_id="ChEBI:CHEBI:58095"
FT /evidence="ECO:0000250|UniProtKB:Q9Y285"
SQ SEQUENCE 569 AA; 66323 MW; C9704885247FA1E8 CRC64;
MQAKAQEEQK GEELSQFLQA LEEEFALCQE GGGDKREADG PSLENAEAEE LANRRAYYLQ
LKEERNVLVE ESKHVTSLHM SSKHNIEHAK VLGMAKKLET LYYVVNHVRS FNTYQLTEEG
KEYLRDGSPE HVTLRYVMEQ EGCTLEDLKK LFGKKGEIGL NINLKKKKIE LRKSDKRLFP
HVEGSAHSLV DETRCYLQKV EAHGNDEGAL VSHLKGILPP EKGEKKEEDE ANNLIKELKK
RKLIEAKKIS YIYIIRTNLF TKEIKKQITD LTYLLIKNEE YKKYQVKKYN FFSSGKKMNK
GNIHLLIRQM RTFKDVFVSL GFEEMNTHNY VESSFWCFDA LYIPQQHPSR DLQDTFFIKV
PEMCQEEFTD QSYIENVKRV HSVGDYGSFG WNYQWELKST KKNVLRTHTT ANSCRALFQL
AKEYQKTGSI IPKKFFSIDR VFRNENLDST HLAEFHQVEG LIIDRNLGLS HLIGTLSAFY
KYIGISKLRF KPTFNPYTEP SMEVYGYHEE NKKWLEVGNS GIFRPEMLRA MGFPPEVSVI
AWGLSLERPT MIKYSIRNIR DLFGYRSVI
