MBTA_MYCTU
ID MBTA_MYCTU Reviewed; 565 AA.
AC P71716; F2GI64; I6Y957; Q7D787;
DT 07-NOV-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Salicyl-AMP ligase / salicyl-S-ArCP synthetase {ECO:0000305};
DE EC=6.2.1.- {ECO:0000269|PubMed:9831524};
DE AltName: Full=Mycobactin biosynthesis protein MbtA {ECO:0000305};
DE AltName: Full=Salicyl-AMP ligase {ECO:0000303|PubMed:9831524};
DE Short=Sal-AMP ligase {ECO:0000303|PubMed:9831524};
DE EC=2.7.7.- {ECO:0000269|PubMed:17181146, ECO:0000269|PubMed:9831524};
DE AltName: Full=Salicyl-S-ArCP synthetase {ECO:0000303|PubMed:9831524};
GN Name=mbtA {ECO:0000303|PubMed:9831524};
GN OrderedLocusNames=Rv2384 {ECO:0000312|EMBL:CCP45172.1};
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 FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RC STRAIN=CSU93;
RX PubMed=9831524; DOI=10.1016/s1074-5521(98)90291-5;
RA Quadri L.E.N., Sello J., Keating T.A., Weinreb P.H., Walsh C.T.;
RT "Identification of a Mycobacterium tuberculosis gene cluster encoding the
RT biosynthetic enzymes for assembly of the virulence-conferring siderophore
RT mycobactin.";
RL Chem. Biol. 5:631-645(1998).
RN [3]
RP INDUCTION.
RX PubMed=11722747; DOI=10.1046/j.1365-2958.2001.02684.x;
RA Gold B., Rodriguez G.M., Marras S.A.E., Pentecost M., Smith I.;
RT "The Mycobacterium tuberculosis IdeR is a dual functional regulator that
RT controls transcription of genes involved in iron acquisition, iron storage
RT and survival in macrophages.";
RL Mol. Microbiol. 42:851-865(2001).
RN [4]
RP ACTIVITY REGULATION, AND PATHWAY.
RX PubMed=16407990; DOI=10.1038/nchembio706;
RA Ferreras J.A., Ryu J.S., Di Lello F., Tan D.S., Quadri L.E.;
RT "Small-molecule inhibition of siderophore biosynthesis in Mycobacterium
RT tuberculosis and Yersinia pestis.";
RL Nat. Chem. Biol. 1:29-32(2005).
RN [5]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP PATHWAY.
RX PubMed=17181146; DOI=10.1021/jm061068d;
RA Somu R.V., Wilson D.J., Bennett E.M., Boshoff H.I., Celia L., Beck B.J.,
RA Barry C.E. III, Aldrich C.C.;
RT "Antitubercular nucleosides that inhibit siderophore biosynthesis: SAR of
RT the glycosyl domain.";
RL J. Med. Chem. 49:7623-7635(2006).
RN [6]
RP ACTIVITY REGULATION.
RX PubMed=17967002; DOI=10.1021/jm070905o;
RA Qiao C., Gupte A., Boshoff H.I., Wilson D.J., Bennett E.M., Somu R.V.,
RA Barry C.E. III, Aldrich C.C.;
RT "5'-O-[(N-acyl)sulfamoyl]adenosines as antitubercular agents that inhibit
RT MbtA: an adenylation enzyme required for siderophore biosynthesis of the
RT mycobactins.";
RL J. Med. Chem. 50:6080-6094(2007).
RN [7] {ECO:0007744|PubMed:21969609}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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: Involved in the initial steps of the mycobactin biosynthetic
CC pathway. Catalyzes the salicylation of the aryl carrier protein (ArCP)
CC domain of MbtB through a two-step reaction. The first step is the ATP-
CC dependent adenylation of salicylate to generate a salicyl-AMP
CC intermediate. The second step is the transfer of this activated
CC salicylate to MbtB to form a salicyl-ArCP domain thioester.
CC {ECO:0000269|PubMed:9831524}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H(+) + salicylate = 2-hydroxybenzoyl-5'-AMP +
CC diphosphate; Xref=Rhea:RHEA:46704, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:30762, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:86458; Evidence={ECO:0000269|PubMed:17181146,
CC ECO:0000269|PubMed:9831524};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxybenzoyl-5'-AMP + holo-[non-ribosomal peptide
CC synthase] = AMP + H(+) + salicyl-[non-ribosomal peptide synthase];
CC Xref=Rhea:RHEA:46708, Rhea:RHEA-COMP:15309, Rhea:RHEA-COMP:16647,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:64479, ChEBI:CHEBI:86458,
CC ChEBI:CHEBI:86464, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:9831524};
CC -!- ACTIVITY REGULATION: Inhibited by salicyl-AMS, an acyl-AMP analog
CC (PubMed:16407990, PubMed:17181146). Also inhibited by 5'-O-[(N-
CC acyl)sulfamoyl]adenosines (PubMed:17967002).
CC {ECO:0000269|PubMed:16407990, ECO:0000269|PubMed:17181146,
CC ECO:0000269|PubMed:17967002}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9 uM for salicylic acid {ECO:0000269|PubMed:9831524};
CC KM=3.3 uM for salicylic acid {ECO:0000269|PubMed:17181146};
CC KM=184 uM for ATP {ECO:0000269|PubMed:17181146};
CC Note=kcat is 42.7 min(-1) for the adenylation reaction.
CC {ECO:0000269|PubMed:9831524};
CC -!- PATHWAY: Siderophore biosynthesis; mycobactin biosynthesis.
CC {ECO:0000269|PubMed:16407990, ECO:0000269|PubMed:17181146,
CC ECO:0000269|PubMed:9831524}.
CC -!- INDUCTION: Induced by iron starvation conditions. Transcriptionally
CC repressed by IdeR and iron. {ECO:0000269|PubMed:11722747}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP45172.1; -; Genomic_DNA.
DR RefSeq; NP_216900.1; NC_000962.3.
DR RefSeq; WP_003412282.1; NZ_NVQJ01000029.1.
DR AlphaFoldDB; P71716; -.
DR SMR; P71716; -.
DR STRING; 83332.Rv2384; -.
DR BindingDB; P71716; -.
DR ChEMBL; CHEMBL5662; -.
DR SwissLipids; SLP:000001282; -.
DR PaxDb; P71716; -.
DR DNASU; 885833; -.
DR GeneID; 885833; -.
DR KEGG; mtu:Rv2384; -.
DR PATRIC; fig|83332.111.peg.2658; -.
DR TubercuList; Rv2384; -.
DR eggNOG; COG1021; Bacteria.
DR OMA; PMSPHDE; -.
DR PhylomeDB; P71716; -.
DR BioCyc; MetaCyc:G185E-6610-MON; -.
DR UniPathway; UPA00011; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016878; F:acid-thiol ligase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016779; F:nucleotidyltransferase activity; IDA:UniProtKB.
DR GO; GO:0010106; P:cellular response to iron ion starvation; IEP:MTBBASE.
DR GO; GO:0019290; P:siderophore biosynthetic process; IDA:UniProtKB.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Ligase; Nucleotide-binding; Reference proteome; Transferase.
FT CHAIN 1..565
FT /note="Salicyl-AMP ligase / salicyl-S-ArCP synthetase"
FT /id="PRO_0000445644"
FT BINDING 214
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40871"
FT BINDING 330
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40871"
FT BINDING 352
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40871"
FT BINDING 436
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40871"
FT BINDING 451
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40871"
FT BINDING 542
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P40871"
SQ SEQUENCE 565 AA; 59281 MW; CA4DC0FB98384730 CRC64;
MPPKAADGRR PSPDGGLGGF VPFPADRAAS YRAAGYWSGR TLDTVLSDAA RRWPDRLAVA
DAGDRPGHGG LSYAELDQRA DRAAAALHGL GITPGDRVLL QLPNGCQFAV ALFALLRAGA
IPVMCLPGHR AAELGHFAAV SAATGLVVAD VASGFDYRPM ARELVADHPT LRHVIVDGDP
GPFVSWAQLC AQAGTGSPAP PADPGSPALL LVSGGTTGMP KLIPRTHDDY VFNATASAAL
CRLSADDVYL VVLAAGHNFP LACPGLLGAM TVGATAVFAP DPSPEAAFAA IERHGVTVTA
LVPALAKLWA QSCEWEPVTP KSLRLLQVGG SKLEPEDARR VRTALTPGLQ QVFGMAEGLL
NFTRIGDPPE VVEHTQGRPL CPADELRIVN ADGEPVGPGE EGELLVRGPY TLNGYFAAER
DNERCFDPDG FYRSGDLVRR RDDGNLVVTG RVKDVICRAG ETIAASDLEE QLLSHPAIFS
AAAVGLPDQY LGEKICAAVV FAGAPITLAE LNGYLDRRGV AAHTRPDQLV AMPALPTTPI
GKIDKRAIVR QLGIATGPVT TQRCH
