ID   SYI1_PSEFL              Reviewed;         943 AA.
AC   P18330;
DT   01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 2.
DT   02-SEP-2026, entry version 145.
DE   RecName: Full=Isoleucine--tRNA ligase 1;
DE            EC=6.1.1.5;
DE   AltName: Full=Isoleucyl-tRNA synthetase 1;
DE            Short=IleRS 1;
GN   Name=ileS1; Synonyms=ileS;
OS   Pseudomonas fluorescens.
OC   Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria;
OC   Pseudomonadales; Pseudomonadaceae; Pseudomonas.
OX   NCBI_TaxID=294;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 49323 / NCIMB 10586;
RX   PubMed=7929087; DOI=10.1016/s0021-9258(19)51082-1;
RA   Yanagisawa T., Lee J.T., Wu H.C., Kawakami M.;
RT   "Relationship of protein structure of isoleucyl-tRNA synthetase with
RT   pseudomonic acid resistance of Escherichia coli. A proposed mode of action
RT   of pseudomonic acid as an inhibitor of isoleucyl-tRNA synthetase.";
RL   J. Biol. Chem. 269:24304-24309(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29 AND 701-943.
RC   STRAIN=ATCC 49323 / NCIMB 10586;
RX   PubMed=2121716; DOI=10.1128/jb.172.11.6512-6517.1990;
RA   Isaki L., Beers R., Wu H.C.;
RT   "Nucleotide sequence of the Pseudomonas fluorescens signal peptidase II
RT   gene (lsp) and flanking genes.";
RL   J. Bacteriol. 172:6512-6517(1990).
RN   [3]
RP   RESISTANCE TO MUPIROCIN.
RC   STRAIN=ATCC 49323 / NCIMB 10586;
RX   PubMed=12672810; DOI=10.1074/jbc.m302633200;
RA   Yanagisawa T., Kawakami M.;
RT   "How does Pseudomonas fluorescens avoid suicide from its antibiotic
RT   pseudomonic acid? Evidence for two evolutionarily distinct isoleucyl-tRNA
RT   synthetases conferring self-defense.";
RL   J. Biol. Chem. 278:25887-25894(2003).
CC   -!- FUNCTION: Catalyzes the attachment of isoleucine to tRNA(Ile). As IleRS
CC       can inadvertently accommodate and process structurally similar amino
CC       acids such as valine, to avoid such errors it has two additional
CC       distinct tRNA(Ile)-dependent editing activities. One activity is
CC       designated as 'pretransfer' editing and involves the hydrolysis of
CC       activated Val-AMP. The other activity is designated 'posttransfer'
CC       editing and involves deacylation of mischarged Val-tRNA(Ile) (By
CC       similarity). {ECO:0000250}.
CC   -!- FUNCTION: Confers resistance to the antibiotic mupirocin (pseudomonic
CC       acid A), an Ile-analog produced by P.fluorescens NCIMB 10586 itself
CC       that competitively inhibits activation by Ile-tRNA synthetase, thus
CC       inhibiting protein biosynthesis.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=tRNA(Ile) + L-isoleucine + ATP = L-isoleucyl-tRNA(Ile) + AMP +
CC         diphosphate; Xref=Rhea:RHEA:11060, Rhea:RHEA-COMP:9666, Rhea:RHEA-
CC         COMP:9695, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58045,
CC         ChEBI:CHEBI:78442, ChEBI:CHEBI:78528, ChEBI:CHEBI:456215; EC=6.1.1.5;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- SUBUNIT: Monomer.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- DOMAIN: IleRS has two distinct active sites: one for aminoacylation and
CC       one for editing. The misactivated valine is translocated from the
CC       active site to the editing site, which sterically excludes the
CC       correctly activated isoleucine. The single editing site contains two
CC       valyl binding pockets, one specific for each substrate (Val-AMP or Val-
CC       tRNA(Ile)) (By similarity). {ECO:0000250}.
CC   -!- MISCELLANEOUS: P.fluorescens NCIMB 10586 possesses two distinct IleRSs
CC       (IleRS-R1 and IleRS-R2), each with a different level of sensitivity to
CC       mupirocin. Purified IleRs-R2 shows no sensitivity to mupirocin even at
CC       a concentration of 5 mM, 100'000 fold higher than the Ki value of
CC       IleRS-R1.
CC   -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family.
CC       IleS type 1 subfamily. {ECO:0000305}.
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DR   EMBL; X80132; CAA56431.1; -; Genomic_DNA.
DR   EMBL; M35366; AAA25883.1; -; Genomic_DNA.
DR   EMBL; M35367; AAA26022.1; ALT_SEQ; Genomic_DNA.
DR   PIR; A37152; A37152.
DR   AlphaFoldDB; P18330; -.
DR   SMR; P18330; -.
DR   eggNOG; COG0060; Bacteria.
DR   SABIO-RK; P18330; -.
DR   GO; GO:0005829; C:cytosol; IEA:TreeGrafter.
DR   GO; GO:0002161; F:aminoacyl-tRNA deacylase activity; IEA:InterPro.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0004822; F:isoleucine-tRNA ligase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0000049; F:tRNA binding; IEA:InterPro.
DR   GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0006428; P:isoleucyl-tRNA aminoacylation; IEA:UniProtKB-UniRule.
DR   CDD; cd07960; Anticodon_Ia_Ile_BEm; 1.
DR   FunFam; 1.10.730.20:FF:000001; Isoleucine--tRNA ligase; 1.
DR   FunFam; 3.40.50.620:FF:000042; Isoleucine--tRNA ligase; 1.
DR   FunFam; 3.40.50.620:FF:000048; Isoleucine--tRNA ligase; 1.
DR   Gene3D; 1.10.730.20; -; 1.
DR   Gene3D; 3.40.50.620; HUPs; 2.
DR   Gene3D; 3.90.740.10; Valyl/Leucyl/Isoleucyl-tRNA synthetase, editing domain; 1.
DR   HAMAP; MF_02002; Ile_tRNA_synth_type1; 1.
DR   InterPro; IPR001412; aa-tRNA-synth_I_CS.
DR   InterPro; IPR002300; aa-tRNA-synth_Ia.
DR   InterPro; IPR033708; Anticodon_Ile_BEm.
DR   InterPro; IPR002301; Ile-tRNA-ligase.
DR   InterPro; IPR023585; Ile-tRNA-ligase_type1.
DR   InterPro; IPR050081; Ile-tRNA_ligase.
DR   InterPro; IPR013155; M/V/L/I-tRNA-synth_anticd-bd.
DR   InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR   InterPro; IPR009080; tRNAsynth_Ia_anticodon-bd.
DR   InterPro; IPR009008; Val/Leu/Ile-tRNA-synth_edit.
DR   InterPro; IPR010663; Znf_FPG/IleRS.
DR   NCBIfam; TIGR00392; ileS; 1.
DR   PANTHER; PTHR42765:SF1; ISOLEUCINE--TRNA LIGASE, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR42765; SOLEUCYL-TRNA SYNTHETASE; 1.
DR   Pfam; PF08264; Anticodon_1; 1.
DR   Pfam; PF00133; tRNA-synt_1; 1.
DR   Pfam; PF06827; zf-FPG_IleRS; 1.
DR   PRINTS; PR00984; TRNASYNTHILE.
DR   SUPFAM; SSF47323; Anticodon-binding domain of a subclass of class I aminoacyl-tRNA synthetases; 1.
DR   SUPFAM; SSF52374; Nucleotidylyl transferase; 1.
DR   SUPFAM; SSF50677; ValRS/IleRS/LeuRS editing domain; 1.
DR   PROSITE; PS00178; AA_TRNA_LIGASE_I; 1.
PE   3: Inferred from homology;
KW   Aminoacyl-tRNA synthetase; Antibiotic resistance; ATP-binding; Cytoplasm;
KW   Ligase; Metal-binding; Nucleotide-binding; Protein biosynthesis; Zinc.
FT   CHAIN           1..943
FT                   /note="Isoleucine--tRNA ligase 1"
FT                   /id="PRO_0000098445"
FT   MOTIF           58..68
FT                   /note="'HIGH' region"
FT   MOTIF           608..612
FT                   /note="'KMSKS' region"
FT   BINDING         567
FT                   /ligand="L-isoleucyl-5'-AMP"
FT                   /ligand_id="ChEBI:CHEBI:178002"
FT                   /evidence="ECO:0000250"
FT   BINDING         611
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         906
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         909
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         926
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         929
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        28..29
FT                   /note="IL -> SC (in Ref. 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        755..756
FT                   /note="QT -> DR (in Ref. 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        758..759
FT                   /note="LY -> VP (in Ref. 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        761..764
FT                   /note="ISEA -> QRR (in Ref. 2)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   943 AA;  105719 MW;  6827B2BF2EB89FC0 CRC64;
     MTDYKATLNL PDTAFPMKAG LPQREPQILQ RWNSIGLYGK LREIGKDRPK FVLHDGPPYA
     NGTIHIGHAL NKILKDMILR SKTLSGFDAP YVPGWDCHGL PIEHKVEVTY GKNLGADKTR
     ELCRAYATEQ IEGQKSEFIR LGVLGEWDNP YKTMNFKNEA GEIRALAEIV KGGFVFKGLK
     PVNWCFDCGS ALAEAEVEYE DKKSSTIDVA FPIADDAKLA EAFGLASLAK PAAIVIWTTT
     PWTIPANQAL NVHPEFTYAL VDVGDRLLVL AEEMVESCLA RYELQGSVIA TATGSALELI
     NFRHPFYDRL SPVYLADYVE LGSGTGIVHC SPAYGVDDFV ICKKYGMVND DIINPVQSNG
     VYVPSLEFFG GQFIFKADQP IIEKLREVGA LMQTAAIQHS YMHCWRHKTP LIYRATAQWF
     IGMDKEPTSG DTLRVRSLKA IEDTKFVPSW GQARLHSMIA NRPDWCISRQ RNWGVPIPFF
     LNKESGELHP RTVELMEVVA QRVEQQGIEA WFKLDAAELL GDEAPLYDKI SDTLDVWFDS
     GTTHWHVLRG SHPMGHETGP RADLYLEGSD QHRGWFHSSL LTGCAIDNHA PYRELLTHGF
     TVDETGRKMS KSLKNVIEPK KINDTLGADI MRLWVASTDY SGEIAVSDQI LARSADAYRR
     IRNTARFMLS NLTGFNPASD LLPAEDMLAL DRWAVDRTLL LQRELQEHYG EYRFWNVYSK
     IHNFCVQELG GFYLDIIKDR QYTTGANSKA RRSAQTALYH ISEALVRWIA PILAFTADEL
     WEYLPGERNE SVMLNTWYEG LTELPADFEL GREYWEGVMA VKVAVNKELE VQRAAKAVGG
     NLQAEVTLFA EDGLTADLAK LSNELRFVLI TSTASLAPFT QAPADAVATE VPGLKLKVVK
     SAFPKCARCW HCREDVGVNP EHPEICGRCV DNISGEGEVR HYA
//