MBTB_MYCTU
ID MBTB_MYCTU Reviewed; 1414 AA.
AC P9WQ63; L0TCD0; P71717; Q7D788;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Phenyloxazoline synthase MbtB;
DE EC=6.3.2.-;
DE AltName: Full=Mycobactin synthetase protein B;
GN Name=mbtB; OrderedLocusNames=Rv2383c;
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 ROLE IN MYCOBACTIN BIOSYNTHESIS.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=10655517; DOI=10.1073/pnas.97.3.1252;
RA De Voss J.J., Rutter K., Schroeder B.G., Su H., Zhu Y., Barry C.E. III;
RT "The salicylate-derived mycobactin siderophores of Mycobacterium
RT tuberculosis are essential for growth in macrophages.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:1252-1257(2000).
RN [3]
RP INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
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 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: Involved in the initial steps of the mycobactin biosynthetic
CC pathway. Putatively couples activated salicylic acid with serine or
CC threonine and cyclizes this precursor to the hydroxyphenyloxazoline
CC ring system present in this class of siderophores. Essential for growth
CC in macrophages. {ECO:0000269|PubMed:10655517}.
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250};
CC Note=Binds 2 phosphopantetheines covalently. {ECO:0000250};
CC -!- PATHWAY: Siderophore biosynthesis; mycobactin biosynthesis.
CC -!- INDUCTION: Induced by iron starvation conditions and during infection
CC of human THP-1 macrophages. Transcriptionally repressed by IdeR and
CC iron. {ECO:0000269|PubMed:11722747}.
CC -!- DOMAIN: Modular protein that contains an aryl carrier protein (ArCP)
CC domain which bears a phosphopantetheinyl arm to attach the activated
CC salicylic acid, a condensation/cyclization domain involved in the
CC formation of the oxazoline ring, an adenylation domain which activates
CC the serine or threonine residue into an aminoacyl-AMP ester, a peptidyl
CC carrier protein (PCP) domain which bears a phosphopantetheinyl arm to
CC attach the activated serine or threonine, and a terminal thioesterase
CC domain which assists in the transfer of intermediates from MbtB to ACP1
CC in MbtD. {ECO:0000250}.
CC -!- PTM: 4'-phosphopantetheine is transferred from CoA to a specific serine
CC in each of the two carrier protein domains, leading to their activation
CC from apo to holo forms. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC MbtB subfamily. {ECO:0000305}.
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DR EMBL; AL123456; CCP45171.1; -; Genomic_DNA.
DR PIR; B70674; B70674.
DR RefSeq; NP_216899.1; NC_000962.3.
DR RefSeq; WP_003899299.1; NZ_NVQJ01000029.1.
DR AlphaFoldDB; P9WQ63; -.
DR SMR; P9WQ63; -.
DR STRING; 83332.Rv2383c; -.
DR ESTHER; myctu-MBTB; Thioesterase.
DR PaxDb; P9WQ63; -.
DR DNASU; 885838; -.
DR GeneID; 885838; -.
DR KEGG; mtu:Rv2383c; -.
DR PATRIC; fig|83332.111.peg.2657; -.
DR TubercuList; Rv2383c; -.
DR eggNOG; COG1020; Bacteria.
DR eggNOG; COG3208; Bacteria.
DR OMA; MNTVEFI; -.
DR PhylomeDB; P9WQ63; -.
DR BioCyc; MetaCyc:G185E-6609-MON; -.
DR UniPathway; UPA00011; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0000036; F:acyl carrier activity; IDA:MTBBASE.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IDA:MTBBASE.
DR GO; GO:0019540; P:catechol-containing siderophore biosynthetic process; IMP:MTBBASE.
DR GO; GO:0010106; P:cellular response to iron ion starvation; IEP:MTBBASE.
DR GO; GO:0052572; P:response to host immune response; IEP:MTBBASE.
DR GO; GO:0019290; P:siderophore biosynthetic process; IMP:UniProtKB.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR001031; Thioesterase.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF00550; PP-binding; 2.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF53474; SSF53474; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Ligase; Multifunctional enzyme; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..1414
FT /note="Phenyloxazoline synthase MbtB"
FT /id="PRO_0000261306"
FT DOMAIN 5..78
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1057..1135
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 96..394
FT /note="Condensation/cyclization"
FT /evidence="ECO:0000250"
FT REGION 579..975
FT /note="Adenylation"
FT /evidence="ECO:0000250"
FT REGION 1188..1413
FT /note="Thioesterase"
FT /evidence="ECO:0000250"
FT MOD_RES 39
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1094
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1414 AA; 151634 MW; CB31307EF6CB1039 CRC64;
MVHATACSEI IRAEVAELLG VRADALHPGA NLVGQGLDSI RMMSLVGRWR RKGIAVDFAT
LAATPTIEAW SQLVSAGTGV APTAVAAPGD AGLSQEGEPF PLAPMQHAMW VGRHDHQQLG
GVAGHLYVEF DGARVDPDRL RAAATRLALR HPMLRVQFLP DGTQRIPPAA GSRDFPISVA
DLRHVAPDVV DQRLAGIRDA KSHQQLDGAV FELALTLLPG ERTRLHVDLD MQAADAMSYR
ILLADLAALY DGREPPALGY TYREYRQAIE AEETLPQPVR DADRDWWAQR IPQLPDPPAL
PTRAGGERDR RRSTRRWHWL DPQTRDALFA RARARGITPA MTLAAAFANV LARWSASSRF
LLNLPLFSRQ ALHPDVDLLV GDFTSSLLLD VDLTGARTAA ARAQAVQEAL RSAAGHSAYP
GLSVLRDLSR HRGTQVLAPV VFTSALGLGD LFCPDVTEQF GTPGWIISQG PQVLLDAQVT
EFDGGVLVNW DVREGVFAPG VIDAMFTHQV DELLRLAAGD DAWDAPSPSA LPAAQRAVRA
ALNGRTAAPS TEALHDGFFR QAQQQPDAPA VFASSGDLSY AQLRDQASAV AAALRAAGLR
VGDTVAVLGP KTGEQVAAVL GILAAGGVYL PIGVDQPRDR AERILATGSV NLALVCGPPC
QVRVPVPTLL LADVLAAAPA EFVPGPSDPT ALAYVLFTSG STGEPKGVEV AHDAAMNTVE
TFIRHFELGA ADRWLALATL ECDMSVLDIF AALRSGGAIV VVDEAQRRDP DAWARLIDTY
EVTALNFMPG WLDMLLEVGG GRLSSLRAVA VGGDWVRPDL ARRLQVQAPS ARFAGLGGAT
ETAVHATIFE VQDAANLPPD WASVPYGVPF PNNACRVVAD SGDDCPDWVA GELWVSGRGI
ARGYRGRPEL TAERFVEHDG RTWYRTGDLA RYWHDGTLEF VGRADHRVKI SGYRVELGEI
EAALQRLPGV HAAAATVLPG GSDVLAAAVC VDDAGVTAES IRQQLADLVP AHMIPRHVTL
LDRIPFTDSG KIDRAEVGAL LAAEVERSGD RSAPYAAPRT VLQRALRRIV ADILGRANDA
VGVHDDFFAL GGDSVLATQV VAGIRRWLDS PSLMVADMFA ARTIAALAQL LTGREANADR
LELVAEVYLE IANMTSADVM AALDPIEQPA QPAFKPWVKR FTGTDKPGAV LVFPHAGGAA
AAYRWLAKSL VANDVDTFVV QYPQRADRRS HPAADSIEAL ALELFEAGDW HLTAPLTLFG
HCMGAIVAFE FARLAERNGV PVRALWASSG QAPSTVAASG PLPTADRDVL ADMVDLGGTD
PVLLEDEEFV ELLVPAVKAD YRALSGYSCP PDVRIRANIH AVGGNRDHRI SREMLTSWET
HTSGRFTLSH FDGGHFYLND HLDAVARMVS ADVR
