SYT_METJA
ID SYT_METJA Reviewed; 620 AA.
AC Q58597;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Threonine--tRNA ligase {ECO:0000255|HAMAP-Rule:MF_00184};
DE EC=6.1.1.3 {ECO:0000255|HAMAP-Rule:MF_00184};
DE AltName: Full=Threonyl-tRNA synthetase {ECO:0000255|HAMAP-Rule:MF_00184, ECO:0000303|PubMed:15240874};
DE Short=ThrRS {ECO:0000255|HAMAP-Rule:MF_00184};
GN Name=thrS {ECO:0000255|HAMAP-Rule:MF_00184, ECO:0000303|PubMed:15240874};
GN OrderedLocusNames=MJ1197;
OS Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM
OS 10045 / NBRC 100440) (Methanococcus jannaschii).
OC Archaea; Euryarchaeota; Methanomada group; Methanococci; Methanococcales;
OC Methanocaldococcaceae; Methanocaldococcus.
OX NCBI_TaxID=243232;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=8688087; DOI=10.1126/science.273.5278.1058;
RA Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G.,
RA Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R.,
RA Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R.,
RA Kirkness E.F., Weinstock K.G., Merrick J.M., Glodek A., Scott J.L.,
RA Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R.,
RA Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D.,
RA Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P.,
RA Fraser C.M., Smith H.O., Woese C.R., Venter J.C.;
RT "Complete genome sequence of the methanogenic archaeon, Methanococcus
RT jannaschii.";
RL Science 273:1058-1073(1996).
RN [2]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF HIS-7; PHE-13;
RP ASP-46; HIS-80; LYS-118; CYS-124; HIS-127 AND ARG-134.
RX PubMed=15240874; DOI=10.1073/pnas.0403926101;
RA Korencic D., Ahel I., Schelert J., Sacher M., Ruan B., Stathopoulos C.,
RA Blum P., Ibba M., Soell D.;
RT "A freestanding proofreading domain is required for protein synthesis
RT quality control in Archaea.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10260-10265(2004).
RN [3]
RP FUNCTION, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15507440; DOI=10.1074/jbc.m411039200;
RA Ruan B., Bovee M.L., Sacher M., Stathopoulos C., Poralla K.,
RA Francklyn C.S., Soell D.;
RT "A unique hydrophobic cluster near the active site contributes to
RT differences in borrelidin inhibition among threonyl-tRNA synthetases.";
RL J. Biol. Chem. 280:571-577(2005).
RN [4] {ECO:0007744|PDB:4RRF, ECO:0007744|PDB:4RRG}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 1-141 (EDITING DOMAIN) IN COMPLEX
RP WITH POST-TRANSFER EDITING SUBSTRATE ANALOGS, FUNCTION, EDITING REACTION
RP MECHANISM, AND MUTAGENESIS OF TYR-117; LYS-118 AND GLU-131.
RX PubMed=26113036; DOI=10.1038/ncomms8552;
RA Ahmad S., Muthukumar S., Kuncha S.K., Routh S.B., Yerabham A.S.,
RA Hussain T., Kamarthapu V., Kruparani S.P., Sankaranarayanan R.;
RT "Specificity and catalysis hardwired at the RNA-protein interface in a
RT translational proofreading enzyme.";
RL Nat. Commun. 6:7552-7552(2015).
CC -!- FUNCTION: Catalyzes the attachment of threonine to tRNA(Thr) in a two-
CC step reaction: L-threonine is first activated by ATP to form Thr-AMP
CC and then transferred to the acceptor end of tRNA(Thr)
CC (PubMed:15240874). Also activates L-serine, but does not detectably
CC transfer it to tRNA(Thr) (PubMed:15240874). Edits incorrectly charged
CC L-seryl-tRNA(Thr) via its editing domain (PubMed:15240874). Has no
CC activity on correctly acylated L-seryl-tRNA(Ser) or L-threonyl-
CC tRNA(Thr) (PubMed:15240874). Deacylates correctly charged glycyl-
CC tRNA(Gly), but not glycyl-tRNA(Gly)(2'-dA76) (the terminal 2'-OH of
CC tRNA adenine 76 has been dehydroxylated) nor the 2'-fluoro tRNA
CC derivative, strongly suggesting the editing function is tRNA catalyzed
CC (PubMed:26113036). {ECO:0000269|PubMed:15240874,
CC ECO:0000269|PubMed:26113036}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonine + tRNA(Thr) = AMP + diphosphate + H(+) + L-
CC threonyl-tRNA(Thr); Xref=Rhea:RHEA:24624, Rhea:RHEA-COMP:9670,
CC Rhea:RHEA-COMP:9704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57926, ChEBI:CHEBI:78442,
CC ChEBI:CHEBI:78534, ChEBI:CHEBI:456215; EC=6.1.1.3;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00184};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00184};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_00184};
CC -!- ACTIVITY REGULATION: Not inhibited by 1 uM borrelidin (BN); probably
CC does not bind BN. {ECO:0000269|PubMed:15507440}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=25 mM for L-serine activation {ECO:0000269|PubMed:15240874};
CC KM=100 mM for L-threonine activation {ECO:0000269|PubMed:15240874,
CC ECO:0000269|PubMed:15507440};
CC Note=kcat is 12.3 sec(-1) for L-serine, 13.5 for L-threonine at 60
CC degrees Celsius (PubMed:15240874). kcat is 1.2 sec(-1)
CC (PubMed:15507440). {ECO:0000269|PubMed:15240874,
CC ECO:0000269|PubMed:15507440};
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_00184}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00184}.
CC -!- DOMAIN: The N-terminal domain (about residues 1-140) is an archaea-
CC specific tRNA-editing domain (PubMed:15240874, PubMed:26113036) that
CC has a highly similar structure to Dtd (D-aminoacyl-tRNA deacylase).
CC Editing of incorrectly charged L-seryl-tRNA(Thr) by this domain is tRNA
CC catalyzed (PubMed:26113036). {ECO:0000269|PubMed:15240874,
CC ECO:0000269|PubMed:26113036}.
CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC {ECO:0000255|HAMAP-Rule:MF_00184}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB99201.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; L77117; AAB99201.1; ALT_INIT; Genomic_DNA.
DR PIR; D64449; D64449.
DR RefSeq; WP_064496752.1; NC_000909.1.
DR PDB; 4RRF; X-ray; 1.70 A; A/B/C/D/E/F=1-141.
DR PDB; 4RRG; X-ray; 1.93 A; A/B/C/D=1-141.
DR PDBsum; 4RRF; -.
DR PDBsum; 4RRG; -.
DR AlphaFoldDB; Q58597; -.
DR SMR; Q58597; -.
DR STRING; 243232.MJ_1197; -.
DR PRIDE; Q58597; -.
DR DNASU; 1452092; -.
DR EnsemblBacteria; AAB99201; AAB99201; MJ_1197.
DR GeneID; 1452092; -.
DR KEGG; mja:MJ_1197; -.
DR eggNOG; arCOG00401; Archaea.
DR HOGENOM; CLU_029833_0_0_2; -.
DR InParanoid; Q58597; -.
DR OMA; IATFQID; -.
DR OrthoDB; 11656at2157; -.
DR PhylomeDB; Q58597; -.
DR BRENDA; 6.1.1.3; 3260.
DR Proteomes; UP000000805; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0002161; F:aminoacyl-tRNA editing activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004829; F:threonine-tRNA ligase activity; IDA:UniProtKB.
DR GO; GO:0000049; F:tRNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006435; P:threonyl-tRNA aminoacylation; IDA:UniProtKB.
DR CDD; cd00771; ThrRS_core; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR Gene3D; 3.40.50.800; -; 1.
DR Gene3D; 3.50.80.10; -; 1.
DR HAMAP; MF_00184; Thr_tRNA_synth; 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; IPR023509; DTD-like_sf.
DR InterPro; IPR002320; Thr-tRNA-ligase_IIa.
DR InterPro; IPR015011; Threonyl-tRNA_syn_edit_dom_arc.
DR InterPro; IPR033728; ThrRS_core.
DR PANTHER; PTHR11451; PTHR11451; 1.
DR Pfam; PF03129; HGTP_anticodon; 1.
DR Pfam; PF00587; tRNA-synt_2b; 1.
DR Pfam; PF08915; tRNA-Thr_ED; 1.
DR PRINTS; PR01047; TRNASYNTHTHR.
DR SUPFAM; SSF55681; SSF55681; 1.
DR TIGRFAMs; TIGR00418; thrS; 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 Metal-binding; Nucleotide-binding; Protein biosynthesis;
KW Reference proteome; RNA-binding; tRNA-binding; Zinc.
FT CHAIN 1..620
FT /note="Threonine--tRNA ligase"
FT /id="PRO_0000101101"
FT REGION 1..141
FT /note="Editing domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00184,
FT ECO:0000305|PubMed:15240874"
FT REGION 197..496
FT /note="Catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00184"
FT BINDING 289
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00184"
FT BINDING 341
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00184"
FT BINDING 465
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00184"
FT MUTAGEN 7
FT /note="H->A: Still charges Thr, no longer edits mischarged
FT L-seryl-tRNA(Thr)."
FT /evidence="ECO:0000269|PubMed:15240874"
FT MUTAGEN 13
FT /note="F->A: Still charges Thr, 5% editing of mischarged L-
FT seryl-tRNA(Thr)."
FT /evidence="ECO:0000269|PubMed:15240874"
FT MUTAGEN 46
FT /note="D->A: Wild-type for Thr charging and L-seryl-
FT tRNA(Thr) editing."
FT /evidence="ECO:0000269|PubMed:15240874"
FT MUTAGEN 80
FT /note="H->A: Still charges Thr, no longer edits mishcarged
FT L-seryl-tRNA(Thr), high mischarging activity."
FT /evidence="ECO:0000269|PubMed:15240874"
FT MUTAGEN 117
FT /note="Y->A: Isolated domain has nearly wild-type
FT deacylation of mischarged L-seryl-tRNA(Thr), no activity on
FT L-threonyl-tRNA(Thr). Intermediate deacylation of L-seryl-
FT tRNA(Thr); when associated with A-131."
FT /evidence="ECO:0000269|PubMed:26113036"
FT MUTAGEN 118
FT /note="K->A: Still charges Thr, no longer edits mischarged
FT L-seryl-tRNA(Thr)."
FT /evidence="ECO:0000269|PubMed:15240874"
FT MUTAGEN 118
FT /note="K->M: Isolated domain does not deacylate mischarged
FT L-seryl-tRNA(Thr), no activity on L-threonyl-tRNA(Thr)."
FT /evidence="ECO:0000269|PubMed:26113036"
FT MUTAGEN 124
FT /note="C->A: Still charges Thr, 80% editing of mischarged
FT L-seryl-tRNA(Thr), no mischarging activity."
FT /evidence="ECO:0000269|PubMed:15240874"
FT MUTAGEN 127
FT /note="H->A: Still charges Thr, no longer edits mischarged
FT L-seryl-tRNA(Thr), high mischarging activity."
FT /evidence="ECO:0000269|PubMed:15240874"
FT MUTAGEN 131
FT /note="E->A: Isolated domain has almost no deacylation of
FT mischarged L-seryl-tRNA(Thr), no activity on L-threonyl-
FT tRNA(Thr). Intermediate deacylation of L-seryl-tRNA(Thr);
FT when associated with A-117."
FT /evidence="ECO:0000269|PubMed:26113036"
FT MUTAGEN 134
FT /note="R->A: Still charges Thr, 20% editing of mischarged
FT L-seryl-tRNA(Thr)."
FT /evidence="ECO:0000269|PubMed:15240874"
FT STRAND 2..18
FT /evidence="ECO:0007829|PDB:4RRF"
FT STRAND 28..41
FT /evidence="ECO:0007829|PDB:4RRF"
FT HELIX 44..48
FT /evidence="ECO:0007829|PDB:4RRF"
FT HELIX 50..68
FT /evidence="ECO:0007829|PDB:4RRF"
FT STRAND 72..77
FT /evidence="ECO:0007829|PDB:4RRF"
FT HELIX 79..81
FT /evidence="ECO:0007829|PDB:4RRF"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:4RRF"
FT HELIX 88..104
FT /evidence="ECO:0007829|PDB:4RRF"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:4RRF"
FT STRAND 116..124
FT /evidence="ECO:0007829|PDB:4RRF"
FT STRAND 130..135
FT /evidence="ECO:0007829|PDB:4RRF"
SQ SEQUENCE 620 AA; 72357 MW; 514D190E790F64F6 CRC64;
MKMLLIHSDY LEFEAKEKTK IAEETENLKG KLDECLACFI AVEREDENNP EGTAIGAVEE
IEKVANQLKV NNIVVYPYAH LSSDLSSPET AVKVLKDIES ILKERGYNVL RAPFGWYKAF
KISCKGHPLS ELSRKIVAKE EKKEEGEESK FYLLNPETEE IIELNENNIN IIKDEELLAL
AKHELGIREH KEHDEPPHVK FIKEKDICSY EEASDPGHFR WYPKGKLMRD LLADYVYNLV
VNMGAMPVET PIMYDLGNPA IREHADKFGE RQYRFRQGNK ELMLRFAACF GQFMMKKDMY
LLPRYLPLKL YELSTYSFRY EQRGELVGLK RLRCFTMPDM HTVCLNLEQA MEEFEKQFWE
CLKTGDDLNL SYSVIFRFTK DFFDEHRDWF FKIAKEYKNK YGKDVILEIL PKRKHYWVGK
VDIAVIDSLG RPIENPTVQI DVESAKRFDI KVHTNEGEIY PIILHCSPTG SIERVLCGLL
EKAAIEAEKG NAPMLPVWLS PIQVRVIPVA ERHYDYALKV AEKLRENNIR ADFDDREESV
SKKIRNAGKE WVPYVVVIGD EEMESDKLTV TIREKSTLKK PYKEKMTLDE LIERIKKETA
NYPYRPLPLP IRCSLQPKFH
