DTD_PLAF7
ID DTD_PLAF7 Reviewed; 164 AA.
AC Q8IIS0;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=D-aminoacyl-tRNA deacylase;
DE Short=PfDTD {ECO:0000303|PubMed:20445234};
DE EC=3.1.1.96 {ECO:0000269|PubMed:24302572, ECO:0000305|PubMed:20007323};
DE AltName: Full=D-Tyrosyl-tRNA(Tyr) deacylase {ECO:0000303|PubMed:20445234};
DE AltName: Full=Gly-tRNA(Ala) deacylase {ECO:0000303|PubMed:28362257};
DE AltName: Full=Gly-tRNA(Gly) deacylase {ECO:0000303|PubMed:27224426};
GN Name=DTD {ECO:0000303|PubMed:20007323}; ORFNames=PF11_0095, PF3D7_1108200;
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, AND CATALYTIC ACTIVITY.
RX PubMed=28362257; DOI=10.7554/elife.24001;
RA Pawar K.I., Suma K., Seenivasan A., Kuncha S.K., Routh S.B.,
RA Kruparani S.P., Sankaranarayanan R.;
RT "Role of D-aminoacyl-tRNA deacylase beyond chiral proofreading as a
RT cellular defense against glycine mischarging by AlaRS.";
RL Elife 6:0-0(2017).
RN [3] {ECO:0007744|PDB:3LMT, ECO:0007744|PDB:3LMU, ECO:0007744|PDB:3LMV}
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS).
RX PubMed=20445234; DOI=10.1107/s0907444910006062;
RA Yogavel M., Khan S., Bhatt T.K., Sharma A.;
RT "Structure of D-tyrosyl-tRNATyr deacylase using home-source Cu Kalpha and
RT moderate-quality iodide-SAD data: structural polymorphism and HEPES-bound
RT enzyme states.";
RL Acta Crystallogr. D 66:584-592(2010).
RN [4] {ECO:0007744|PDB:3KNF, ECO:0007744|PDB:3KNP, ECO:0007744|PDB:3KO3, ECO:0007744|PDB:3KO4, ECO:0007744|PDB:3KO5, ECO:0007744|PDB:3KO7, ECO:0007744|PDB:3KO9, ECO:0007744|PDB:3KOB, ECO:0007744|PDB:3KOC, ECO:0007744|PDB:3KOD}
RP X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) IN COMPLEX WITH D-AMINO ACIDS,
RP FUNCTION, CATALYTIC ACTIVITY, POSSIBLE REACTION MECHANISM, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=20007323; DOI=10.1074/jbc.m109.038562;
RA Bhatt T.K., Yogavel M., Wydau S., Berwal R., Sharma A.;
RT "Ligand-bound structures provide atomic snapshots for the catalytic
RT mechanism of D-amino acid deacylase.";
RL J. Biol. Chem. 285:5917-5930(2010).
RN [5] {ECO:0007744|PDB:4NBI, ECO:0007744|PDB:4NBJ}
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG,
RP FUNCTION, POSSIBLE REACTION MECHANISM, SUBUNIT, DOMAIN, AND MUTAGENESIS OF
RP SER-87; GLN-88; THR-90; ALA-112; PHE-137; GLY-149 AND PRO-150.
RX PubMed=24302572; DOI=10.7554/elife.01519;
RA Ahmad S., Routh S.B., Kamarthapu V., Chalissery J., Muthukumar S.,
RA Hussain T., Kruparani S.P., Deshmukh M.V., Sankaranarayanan R.;
RT "Mechanism of chiral proofreading during translation of the genetic code.";
RL Elife 2:E01519-E01519(2013).
RN [6] {ECO:0007744|PDB:5J61}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH GLY SUBSTRATE
RP ANALOG, FUNCTION, SUBSTRATE SPECIFICITY, AND MUTAGENESIS OF ALA-112 AND
RP PHE-137.
RX PubMed=27224426; DOI=10.1371/journal.pbio.1002465;
RA Routh S.B., Pawar K.I., Ahmad S., Singh S., Suma K., Kumar M., Kuncha S.K.,
RA Yadav K., Kruparani S.P., Sankaranarayanan R.;
RT "Elongation factor Tu prevents misediting of Gly-tRNA(Gly) caused by the
RT design behind the chiral proofreading site of D-aminoacyl-tRNA deacylase.";
RL PLoS Biol. 14:E1002465-E1002465(2016).
CC -!- FUNCTION: D-aminoacyl-tRNA deacylase, with no observable activity on
CC tRNAs charged with their cognate L-amino acid (PubMed:20007323,
CC PubMed:24302572, PubMed:27224426). Probably acts by rejecting L-amino
CC acids from its binding site rather than specific recognition of D-amino
CC acids (PubMed:27224426). Catalyzes the hydrolysis of D-tyrosyl-
CC tRNA(Tyr), has no activity on correctly charged L-tyrosyl-tRNA(Tyr)
CC (PubMed:20007323, PubMed:24302572, PubMed:27224426). Hydrolyzes
CC correctly charged, achiral, glycyl-tRNA(Gly) (PubMed:27224426).
CC Deacylates mischarged D.melanogaster and E.coli glycyl-tRNA(Ala)
CC (PubMed:28362257). Probably acts via tRNA-based rather than protein-
CC based catalysis (PubMed:24302572, PubMed:27224426). Acts on tRNAs only
CC when the D-amino acid is either attached to the ribose 3'-OH or
CC transferred to the 3'-OH from the 2'-OH through rapid
CC transesterification (PubMed:24302572). Binds a number of other D-amino
CC acids (D-Arg, D-Glu, D-His, D-Lys, D-Ser), suggesting it may also
CC deacylate other mischarged tRNAs (PubMed:20007323).
CC {ECO:0000269|PubMed:20007323, ECO:0000269|PubMed:24302572,
CC ECO:0000269|PubMed:27224426, ECO:0000269|PubMed:28362257}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycyl-tRNA(Ala) + H2O = glycine + H(+) + tRNA(Ala);
CC Xref=Rhea:RHEA:53744, Rhea:RHEA-COMP:9657, Rhea:RHEA-COMP:13640,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57305,
CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78522; EC=3.1.1.96;
CC Evidence={ECO:0000269|PubMed:28362257};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a D-aminoacyl-tRNA + H2O = a D-alpha-amino acid + a tRNA +
CC H(+); Xref=Rhea:RHEA:13953, Rhea:RHEA-COMP:10123, Rhea:RHEA-
CC COMP:10124, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:59871,
CC ChEBI:CHEBI:78442, ChEBI:CHEBI:79333; EC=3.1.1.96;
CC Evidence={ECO:0000269|PubMed:24302572, ECO:0000305|PubMed:20007323};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-tyrosyl-tRNA(Tyr) + H2O = D-tyrosine + tRNA(Tyr);
CC Xref=Rhea:RHEA:25347, Rhea:RHEA-COMP:9707, Rhea:RHEA-COMP:9872,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:58570, ChEBI:CHEBI:78442,
CC ChEBI:CHEBI:78723; Evidence={ECO:0000269|PubMed:20007323,
CC ECO:0000269|PubMed:24302572, ECO:0000269|PubMed:27224426};
CC -!- SUBUNIT: Homodimer (PubMed:20007323, PubMed:24302572).
CC {ECO:0000269|PubMed:20007323, ECO:0000269|PubMed:24302572}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20007323}.
CC -!- DOMAIN: A Gly-cisPro motif from one monomer fits into the active site
CC of the other monomer to allow specific chiral rejection of L-amino
CC acids (PubMed:24302572, PubMed:27224426). {ECO:0000269|PubMed:24302572,
CC ECO:0000269|PubMed:27224426}.
CC -!- MISCELLANEOUS: In the crystal structures with bound ADP (PDB 3KO4,
CC 3KO5), the adenosine moiety is thought to represent the authentic C-
CC terminal adenosine of charged tRNA and is annotated as such in this
CC entry (PubMed:20007323). {ECO:0000305|PubMed:20007323}.
CC -!- SIMILARITY: Belongs to the DTD family.
CC -!- CAUTION: Initially the conserved reside Thr-90 was thought to be a
CC nucleophile; mutagenesis in this organism and E.coli indicates it is
CC not. {ECO:0000269|PubMed:24302572}.
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DR EMBL; LN999945; CZT98748.1; -; Genomic_DNA.
DR RefSeq; XP_001347770.1; XM_001347734.1.
DR PDB; 3KNF; X-ray; 3.00 A; A/B/C/D/E/F=1-164.
DR PDB; 3KNP; X-ray; 3.30 A; A/B/C/D/E/F=1-164.
DR PDB; 3KO3; X-ray; 2.80 A; A/B/C/D/E/F=1-164.
DR PDB; 3KO4; X-ray; 2.70 A; A/B/C/D/E/F=1-164.
DR PDB; 3KO5; X-ray; 2.09 A; A/B/C/D/E/F=1-164.
DR PDB; 3KO7; X-ray; 2.21 A; A/B/C/D/E/F=1-164.
DR PDB; 3KO9; X-ray; 2.75 A; A/B/C/D/E/F=1-164.
DR PDB; 3KOB; X-ray; 2.99 A; A/B/C/D/E/F=1-164.
DR PDB; 3KOC; X-ray; 2.91 A; A/B/C/D/E/F=1-164.
DR PDB; 3KOD; X-ray; 3.00 A; A/B/C/D/E/F=1-164.
DR PDB; 3LMT; X-ray; 2.75 A; A/B/C/D/E/F=1-164.
DR PDB; 3LMU; X-ray; 3.30 A; A/B/C/D/E/F/G/H=1-164.
DR PDB; 3LMV; X-ray; 2.83 A; A/B/C/D/E/F=1-164.
DR PDB; 4NBI; X-ray; 1.86 A; A/B=1-164.
DR PDB; 4NBJ; X-ray; 2.20 A; A/B/C/D/E/F/G/H=1-164.
DR PDB; 5J61; X-ray; 2.10 A; A/B/C/D/E/F/G/H=1-164.
DR PDBsum; 3KNF; -.
DR PDBsum; 3KNP; -.
DR PDBsum; 3KO3; -.
DR PDBsum; 3KO4; -.
DR PDBsum; 3KO5; -.
DR PDBsum; 3KO7; -.
DR PDBsum; 3KO9; -.
DR PDBsum; 3KOB; -.
DR PDBsum; 3KOC; -.
DR PDBsum; 3KOD; -.
DR PDBsum; 3LMT; -.
DR PDBsum; 3LMU; -.
DR PDBsum; 3LMV; -.
DR PDBsum; 4NBI; -.
DR PDBsum; 4NBJ; -.
DR PDBsum; 5J61; -.
DR AlphaFoldDB; Q8IIS0; -.
DR SMR; Q8IIS0; -.
DR STRING; 5833.PF11_0095; -.
DR PRIDE; Q8IIS0; -.
DR EnsemblProtists; CZT98748; CZT98748; PF3D7_1108200.
DR GeneID; 810646; -.
DR KEGG; pfa:PF3D7_1108200; -.
DR VEuPathDB; PlasmoDB:PF3D7_1108200; -.
DR HOGENOM; CLU_076901_0_4_1; -.
DR InParanoid; Q8IIS0; -.
DR OMA; GVFQAHM; -.
DR PhylomeDB; Q8IIS0; -.
DR EvolutionaryTrace; Q8IIS0; -.
DR Proteomes; UP000001450; Chromosome 11.
DR GO; GO:0005737; C:cytoplasm; IDA:GeneDB.
DR GO; GO:0051500; F:D-tyrosyl-tRNA(Tyr) deacylase activity; IDA:UniProtKB.
DR GO; GO:0106026; F:Gly-tRNA(Ala) hydrolase activity; IDA:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0000049; F:tRNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006399; P:tRNA metabolic process; IBA:GO_Central.
DR Gene3D; 3.50.80.10; -; 1.
DR InterPro; IPR003732; Daa-tRNA_deacyls_DTD.
DR InterPro; IPR023509; DTD-like_sf.
DR PANTHER; PTHR10472; PTHR10472; 1.
DR Pfam; PF02580; Tyr_Deacylase; 1.
DR SUPFAM; SSF69500; SSF69500; 1.
DR TIGRFAMs; TIGR00256; TIGR00256; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Hydrolase; Nucleotide-binding; Reference proteome;
KW RNA-binding; tRNA-binding.
FT CHAIN 1..164
FT /note="D-aminoacyl-tRNA deacylase"
FT /id="PRO_0000441703"
FT MOTIF 104..107
FT /note="C-terminal adenosine nucleotide of tRNA"
FT /evidence="ECO:0000305|PubMed:20007323,
FT ECO:0007744|PDB:3KO4, ECO:0007744|PDB:3KO5"
FT MOTIF 149..150
FT /note="Gly-cisPro motif, allows the protein to recognize
FT chirality of D-amino acids"
FT /evidence="ECO:0000269|PubMed:24302572"
FT ACT_SITE 90
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:20007323"
FT BINDING 72
FT /ligand="tRNA"
FT /ligand_id="ChEBI:CHEBI:17843"
FT /ligand_part="AMP 3'-end residue"
FT /ligand_part_id="ChEBI:CHEBI:78442"
FT /evidence="ECO:0000305|PubMed:20007323,
FT ECO:0007744|PDB:3KO5"
FT BINDING 89
FT /ligand="tRNA"
FT /ligand_id="ChEBI:CHEBI:17843"
FT /ligand_part="AMP 3'-end residue"
FT /ligand_part_id="ChEBI:CHEBI:78442"
FT /evidence="ECO:0000305|PubMed:20007323,
FT ECO:0007744|PDB:3KO4, ECO:0007744|PDB:3KO5"
FT MUTAGEN 87
FT /note="S->A: Partial loss of deacylation of D-tyrosyl-
FT tRNA(Tyr)."
FT /evidence="ECO:0000269|PubMed:24302572"
FT MUTAGEN 87
FT /note="S->P: Wild-type deacylation of D-tyrosyl-tRNA(Tyr)."
FT /evidence="ECO:0000269|PubMed:24302572"
FT MUTAGEN 88
FT /note="Q->A,E,N: Wild-type deacylation of D-tyrosyl-
FT tRNA(Tyr)."
FT /evidence="ECO:0000269|PubMed:24302572"
FT MUTAGEN 90
FT /note="T->A,S: Wild-type deacylation of D-tyrosyl-
FT tRNA(Tyr)."
FT /evidence="ECO:0000269|PubMed:24302572"
FT MUTAGEN 112
FT /note="A->F: Loss of deacylation of D-tyrosyl-tRNA(Tyr),
FT loss of deacylation of glycyl-tRNA(Gly), not toxic upon
FT overexpression."
FT /evidence="ECO:0000269|PubMed:24302572,
FT ECO:0000269|PubMed:27224426"
FT MUTAGEN 137
FT /note="F->A: Loss of deacylation of D-tyrosyl-tRNA(Tyr),
FT loss of deacylation of glycyl-tRNA(Gly)."
FT /evidence="ECO:0000269|PubMed:24302572,
FT ECO:0000269|PubMed:27224426"
FT MUTAGEN 149
FT /note="G->A: Loss of deacylation of D-tyrosyl-tRNA(Tyr)."
FT /evidence="ECO:0000269|PubMed:24302572"
FT MUTAGEN 150
FT /note="P->A: Loss of deacylation of D-tyrosyl-tRNA(Tyr)."
FT /evidence="ECO:0000269|PubMed:24302572"
FT STRAND 2..16
FT /evidence="ECO:0007829|PDB:4NBI"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:3KO9"
FT STRAND 27..42
FT /evidence="ECO:0007829|PDB:4NBI"
FT HELIX 49..61
FT /evidence="ECO:0007829|PDB:4NBI"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:3KO5"
FT STRAND 70..74
FT /evidence="ECO:0007829|PDB:3KO5"
FT TURN 76..80
FT /evidence="ECO:0007829|PDB:4NBI"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:4NBI"
FT HELIX 89..92
FT /evidence="ECO:0007829|PDB:4NBI"
FT STRAND 96..100
FT /evidence="ECO:0007829|PDB:4NBI"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:3KO4"
FT HELIX 109..126
FT /evidence="ECO:0007829|PDB:4NBI"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:4NBI"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:4NBI"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:3KOC"
FT STRAND 141..156
FT /evidence="ECO:0007829|PDB:4NBI"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:4NBI"
SQ SEQUENCE 164 AA; 19205 MW; 305B8DA0CFC2508D CRC64;
MRVVIQRVKG AILSVRKENI GENEKELEII SEIKNGLICF LGIHKNDTWE DALYIIRKCL
NLRLWNNDNK TWDKNVKDLN YELLIVSQFT LFGNTKKGNK PDFHLAKEPN EALIFYNKII
DEFKKQYNDD KIKIGKFGNY MNIDVTNDGP VTIYIDTHDI NLNK
