ID   SYI2_STAAU              Reviewed;        1024 AA.
AC   P41368;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   03-AUG-2022, entry version 125.
DE   RecName: Full=Isoleucine--tRNA ligase;
DE            EC=6.1.1.5;
DE   AltName: Full=Isoleucyl-tRNA synthetase;
DE            Short=IleRS;
GN   Name=ileS; Synonyms=mupR;
OS   Staphylococcus aureus.
OG   Plasmid pOX301.
OC   Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=1280;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC   STRAIN=J2870; PLASMID=pOX301;
RX   PubMed=8067768; DOI=10.1128/aac.38.5.1205;
RA   Hodgson J.E., Curnock S.P., Dyke K.G.H., Morris R., Sylvester D.R.,
RA   Gross M.S.;
RT   "Molecular characterization of the gene encoding high-level mupirocin
RT   resistance in Staphylococcus aureus J2870.";
RL   Antimicrob. Agents Chemother. 38:1205-1208(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 504-519 AND 550-609, AND FUNCTION.
RC   STRAIN=J2870;
RX   PubMed=1903747; DOI=10.1016/0378-1097(91)90550-t;
RA   Dyke K.G.H., Curnock S.P., Golding M., Noble W.C.;
RT   "Cloning of the gene conferring resistance to mupirocin in Staphylococcus
RT   aureus.";
RL   FEMS Microbiol. Lett. 61:195-198(1991).
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 high-level resistance to the antibiotic mupirocin
CC       (pseudomonic acid A), an Ile-analog that competitively inhibits
CC       activation by Ile-tRNA synthetase, thus inhibiting protein
CC       biosynthesis. {ECO:0000269|PubMed:1903747, ECO:0000269|PubMed:8067768}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-isoleucine + tRNA(Ile) = AMP + diphosphate + L-
CC         isoleucyl-tRNA(Ile); Xref=Rhea:RHEA:11060, Rhea:RHEA-COMP:9666,
CC         Rhea:RHEA-COMP:9695, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:58045, ChEBI:CHEBI:78442, ChEBI:CHEBI:78528,
CC         ChEBI:CHEBI:456215; EC=6.1.1.5;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC   -!- SUBUNIT: Monomer. {ECO:0000250}.
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   -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family.
CC       IleS type 2 subfamily. {ECO:0000305}.
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DR   EMBL; X75439; CAA53189.1; -; Genomic_DNA.
DR   EMBL; X59478; CAA42080.1; -; Genomic_DNA.
DR   EMBL; X59477; CAA42079.1; -; Genomic_DNA.
DR   RefSeq; WP_012263521.1; NG_056478.1.
DR   RefSeq; YP_001653102.1; NC_010279.1.
DR   AlphaFoldDB; P41368; -.
DR   SMR; P41368; -.
DR   PRIDE; P41368; -.
DR   BRENDA; 6.1.1.5; 3352.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0002161; F:aminoacyl-tRNA editing 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   GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR   CDD; cd07961; Anticodon_Ia_Ile_ABEc; 1.
DR   Gene3D; 3.40.50.620; -; 2.
DR   HAMAP; MF_02003; Ile_tRNA_synth_type2; 1.
DR   InterPro; IPR001412; aa-tRNA-synth_I_CS.
DR   InterPro; IPR002300; aa-tRNA-synth_Ia.
DR   InterPro; IPR033709; Anticodon_Ile_ABEc.
DR   InterPro; IPR002301; Ile-tRNA-ligase.
DR   InterPro; IPR023586; Ile-tRNA-ligase_type2.
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   PANTHER; PTHR42780; PTHR42780; 1.
DR   Pfam; PF08264; Anticodon_1; 1.
DR   Pfam; PF00133; tRNA-synt_1; 1.
DR   PRINTS; PR00984; TRNASYNTHILE.
DR   SUPFAM; SSF47323; SSF47323; 2.
DR   SUPFAM; SSF50677; SSF50677; 1.
DR   TIGRFAMs; TIGR00392; ileS; 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; Plasmid; Protein biosynthesis;
KW   Zinc.
FT   CHAIN           1..1024
FT                   /note="Isoleucine--tRNA ligase"
FT                   /id="PRO_0000098562"
FT   MOTIF           42..52
FT                   /note="'HIGH' region"
FT   MOTIF           585..589
FT                   /note="'KMSKS' region"
FT   BINDING         588
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        519
FT                   /note="P -> R (in Ref. 2; CAA42079)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        591..593
FT                   /note="GNV -> ETF (in Ref. 2; CAA42080)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1024 AA;  118876 MW;  56ECD232CA0C8430 CRC64;
     MTKKYLNTQN EISAFWNTQK IFKKSIDNRK GQESFVFYDG PPTANGLPHA GHVLGRVIKD
     LVARLKTMQG FYVERKAGWD THGLPVELEV EKKIGIKGKQ DIEKYGIENF INECKKSVFN
     YEKEWRDFSK DLGYWVDMDS PYITLENNYI ESVWNILSTF HKKGLLYKGH KVTPYCTHDQ
     TALSSHEVAQ GYKNVKDLSA VVKFQLTNSK DTYFLSWTTT PWTLPANVAL AINKDLNYSK
     IRVENEYYIL ATDLINSIIT EKYEIIDTFS GSNLINLKYI PPFESDGLVN AYYVVDGEFV
     TNSEGTGIVH IAPAHGEDDY QLVLERDLDF LNVITREGVY NDRFPELVGN KAKNSDIEII
     KLLSKKQLLY KKQKYEHNYP HCWRCGNPLI YYAMEGWFIK TTNFKNEIIN NNNNIEWFPS
     HIKEGRMGNF LENMVDWNIG RNRYWGTPLN VWICNDCNHE YAPSSIKDLQ NNSINKIDED
     IELHRPYVDN ITLSCPKCNG KMSRVEEVID VWFDSGSMPF AQHHYPFDNQ KIFNQHFPAD
     FIAEGVDQTR GWFYSLLVIS TILKGKSSYK RALSLGHILD SNGKKMSKSK GNVINPTELI
     NKYGADSLRW ALISDSAPWN NKRFSENIVA QTKSKFIDTL DNIYKFYNMY NKIDHYNPNN
     EITKSRNTLD NWALSRLNTL IKESNIYVNN YDFTSAARLI NEYTNTISNW YIGDSRGRFW
     EQGISNDKKD AYNTLYEILT TLSRLVAPFV PFISEKIHYN LTGKSVHLQD YPQYKESFIN
     QALEDEMHTV IKIVELSRQA RKNADLKIKQ PLSKMVIKPN SQLNLSFLPN YYSIIKDELN
     IKNIELTDNI NDYITYELKL NFSSVGPKLG NKTKNIQTLI DSLSEYDKKS LIESNNFKSL
     SSDAELTKDD FIIKTLPKDS YQLSEDNDCV ILLDKNLSPE LIREGHAREL IRLIQQLRKK
     KNLPINQRID IYIGVTGELL ESIKTNKNMF KENFVIKNIH LNVIDEYENT IHFNNKEIKI
     SLLY