ID   SYI_MYCTU               Reviewed;        1041 AA.
AC   P9WFV3; L0T8J7; O06181; Q10765;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   03-AUG-2022, entry version 46.
DE   RecName: Full=Isoleucine--tRNA ligase;
DE            EC=6.1.1.5;
DE   AltName: Full=Isoleucyl-tRNA synthetase;
DE            Short=IleRS;
GN   Name=ileS; OrderedLocusNames=Rv1536; ORFNames=MTCY48.29c;
OS   Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycobacterium; Mycobacterium tuberculosis complex.
OX   NCBI_TaxID=83332;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=9634230; DOI=10.1038/31159;
RA   Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA   Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA   Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA   Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA   Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA   Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA   Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA   Barrell B.G.;
RT   "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT   genome sequence.";
RL   Nature 393:537-544(1998).
RN   [2]
RP   CATALYTIC ACTIVITY, AND RESISTANCE TO MUPIROCIN.
RX   PubMed=8756461; DOI=10.1021/bi9603027;
RA   Sassanfar M., Kranz J.E., Gallant P., Schimmel P., Shiba K.;
RT   "A eubacterial Mycobacterium tuberculosis tRNA synthetase is eukaryote-like
RT   and resistant to a eubacterial-specific antisynthetase drug.";
RL   Biochemistry 35:9995-10003(1996).
RN   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA   Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA   Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA   Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA   Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT   "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT   mass spectrometry.";
RL   Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
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.
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         Evidence={ECO:0000269|PubMed:8756461};
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; AL123456; CCP44300.1; -; Genomic_DNA.
DR   PIR; E70760; E70760.
DR   RefSeq; NP_216052.1; NC_000962.3.
DR   RefSeq; WP_003407714.1; NZ_NVQJ01000004.1.
DR   AlphaFoldDB; P9WFV3; -.
DR   SMR; P9WFV3; -.
DR   STRING; 83332.Rv1536; -.
DR   PaxDb; P9WFV3; -.
DR   DNASU; 886412; -.
DR   GeneID; 886412; -.
DR   KEGG; mtu:Rv1536; -.
DR   TubercuList; Rv1536; -.
DR   eggNOG; COG0060; Bacteria.
DR   OMA; KMMAPFT; -.
DR   PhylomeDB; P9WFV3; -.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR   GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
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; IMP:MTBBASE.
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; IMP:MTBBASE.
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   Gene3D; 3.90.740.10; -; 1.
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; 1.
DR   SUPFAM; SSF50677; SSF50677; 1.
DR   TIGRFAMs; TIGR00392; ileS; 1.
DR   PROSITE; PS00178; AA_TRNA_LIGASE_I; 1.
PE   1: Evidence at protein level;
KW   Aminoacyl-tRNA synthetase; Antibiotic resistance; ATP-binding; Cytoplasm;
KW   Ligase; Metal-binding; Nucleotide-binding; Protein biosynthesis;
KW   Reference proteome; Zinc.
FT   CHAIN           1..1041
FT                   /note="Isoleucine--tRNA ligase"
FT                   /id="PRO_0000098550"
FT   MOTIF           53..63
FT                   /note="'HIGH' region"
FT   MOTIF           619..623
FT                   /note="'KMSKS' region"
FT   BINDING         622
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   1041 AA;  117340 MW;  B5023822848E08C6 CRC64;
     MTDNAYPKLA GGAPDLPALE LEVLDYWSRD DTFRASIARR DGAPEYVFYD GPPFANGLPH
     YGHLLTGYVK DIVPRYRTMR GYKVERRFGW DTHGLPAELE VERQLGITDK SQIEAMGIAA
     FNDACRASVL RYTDEWQAYV TRQARWVDFD NDYKTLDLAY MESVIWAFKQ LWDKGLAYEG
     YRVLPYCWRD ETPLSNHELR MDDDVYQSRQ DPAVTVGFKV VGGQPDNGLD GAYLLVWTTT
     PWTLPSNLAV AVSPDITYVQ VQAGDRRFVL AEARLAAYAR ELGEEPVVLG TYRGAELLGT
     RYLPPFAYFM DWPNAFQVLA GDFVTTDDGT GIVHMAPAYG EDDMVVAEAV GIAPVTPVDS
     KGRFDVTVAD YQGQHVFDAN AQIVRDLKTQ SGPAAVNGPV LIRHETYEHP YPHCWRCRNP
     LIYRSVSSWF VRVTDFRDRM VELNQQITWY PEHVKDGQFG KWLQGARDWS ISRNRYWGTP
     IPVWKSDDPA YPRIDVYGSL DELERDFGVR PANLHRPYID ELTRPNPDDP TGRSTMRRIP
     DVLDVWFDSG SMPYAQVHYP FENLDWFQGH YPGDFIVEYI GQTRGWFYTL HVLATALFDR
     PAFKTCVAHG IVLGFDGQKM SKSLRNYPDV TEVFDRDGSD AMRWFLMASP ILRGGNLIVT
     EQGIRDGVRQ VLLPLWNTYS FLALYAPKVG TWRVDSVHVL DRYILAKLAV LRDDLSESME
     VYDIPGACEH LRQFTEALTN WYVRRSRSRF WAEDADAIDT LHTVLEVTTR LAAPLLPLIT
     EIIWRGLTRE RSVHLTDWPA PDLLPSDADL VAAMDQVRDV CSAASSLRKA KKLRVRLPLP
     KLIVAVENPQ LLRPFVDLIG DELNVKQVEL TDAIDTYGRF ELTVNARVAG PRLGKDVQAA
     IKAVKAGDGV INPDGTLLAG PAVLTPDEYN SRLVAADPES TAALPDGAGL VVLDGTVTAE
     LEAEGWAKDR IRELQELRKS TGLDVSDRIR VVMSVPAERE DWARTHRDLI AGEILATDFE
     FADLADGVAI GDGVRVSIEK T