ID A85B_MYCTU Reviewed; 325 AA.
AC P9WQP1; D6MJP5; F2GHQ8; P0C5B9; P31952; Q9RMI0;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 27-MAR-2024, entry version 51.
DE RecName: Full=Diacylglycerol acyltransferase/mycolyltransferase Ag85B;
DE Short=DGAT;
DE EC=2.3.1.122;
DE EC=2.3.1.20;
DE AltName: Full=30 kDa extracellular protein;
DE AltName: Full=Acyl-CoA:diacylglycerol acyltransferase;
DE AltName: Full=Antigen 85 complex B;
DE Short=85B;
DE Short=Ag85B;
DE AltName: Full=Extracellular alpha-antigen;
DE AltName: Full=Fibronectin-binding protein B;
DE Short=Fbps B;
DE Flags: Precursor;
GN Name=fbpB; OrderedLocusNames=Rv1886c; ORFNames=MTCY180.32;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=7987013;
RA de Wit L., Palou M., Content J.;
RT "Nucleotide sequence of the 85B-protein gene of Mycobacterium bovis BCG and
RT Mycobacterium tuberculosis.";
RL DNA Seq. 4:267-270(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=8757831; DOI=10.1128/iai.64.8.3038-3047.1996;
RA Harth G., Lee B.Y., Wang J., Clemens D.L., Horwitz M.A.;
RT "Novel insights into the genetics, biochemistry, and immunocytochemistry of
RT the 30-kilodalton major extracellular protein of Mycobacterium
RT tuberculosis.";
RL Infect. Immun. 64:3038-3047(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=BJ10;
RX PubMed=20223296; DOI=10.1016/j.meegid.2010.03.003;
RA Chuang P.C., Chen Y.M., Chen H.Y., Jou R.;
RT "Single nucleotide polymorphisms in cell wall biosynthesis-associated genes
RT and phylogeny of Mycobacterium tuberculosis lineages.";
RL Infect. Genet. Evol. 10:459-466(2010).
RN [4]
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 [5]
RP PROTEIN SEQUENCE OF 41-50.
RX PubMed=2403534; DOI=10.1128/iai.58.1.272-274.1990;
RA Wiker H.G., Sletten K., Nagai S., Harboe M.;
RT "Evidence for three separate genes encoding the proteins of the
RT mycobacterial antigen 85 complex.";
RL Infect. Immun. 58:272-274(1990).
RN [6]
RP FUNCTION IN THE FIBRONECTIN BINDING.
RX PubMed=3141278; DOI=10.1128/iai.56.12.3046-3051.1988;
RA Abou-Zeid C., Ratliff T.L., Wiker H.G., Harboe M., Bennedsen J., Rook G.A.;
RT "Characterization of fibronectin-binding antigens released by Mycobacterium
RT tuberculosis and Mycobacterium bovis BCG.";
RL Infect. Immun. 56:3046-3051(1988).
RN [7]
RP FUNCTION AS A MYCOLYLTRANSFERASE, AND NOMENCLATURE.
RX PubMed=9162010; DOI=10.1126/science.276.5317.1420;
RA Belisle J.T., Vissa V.D., Sievert T., Takayama K., Brennan P.J.,
RA Besra G.S.;
RT "Role of the major antigen of Mycobacterium tuberculosis in cell wall
RT biogenesis.";
RL Science 276:1420-1422(1997).
RN [8]
RP FUNCTION AS A MYCOLYLTRANSFERASE, AND DISRUPTION PHENOTYPE.
RX PubMed=12010501; DOI=10.1046/j.1365-2958.2002.02953.x;
RA Puech V., Guilhot C., Perez E., Tropis M., Armitige L.Y., Gicquel B.,
RA Daffe M.;
RT "Evidence for a partial redundancy of the fibronectin-binding proteins for
RT the transfer of mycoloyl residues onto the cell wall arabinogalactan
RT termini of Mycobacterium tuberculosis.";
RL Mol. Microbiol. 44:1109-1122(2002).
RN [9]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011445;
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).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 41-325 IN COMPLEX WITH SUBSTRATE,
RP ACTIVE SITE, REACTION MECHANISM, AND DISULFIDE BOND.
RX PubMed=11254389; DOI=10.1006/jmbi.2001.4461;
RA Anderson D.H., Harth G., Horwitz M.A., Eisenberg D.;
RT "An interfacial mechanism and a class of inhibitors inferred from two
RT crystal structures of the Mycobacterium tuberculosis 30 kDa major secretory
RT protein (Antigen 85B), a mycolyl transferase.";
RL J. Mol. Biol. 307:671-681(2001).
CC -!- FUNCTION: The antigen 85 proteins (FbpA, FbpB, FbpC) are responsible
CC for the high affinity of mycobacteria for fibronectin, a large adhesive
CC glycoprotein, which facilitates the attachment of M.tuberculosis to
CC murine alveolar macrophages (AMs). They also help to maintain the
CC integrity of the cell wall by catalyzing the transfer of mycolic acids
CC to cell wall arabinogalactan and through the synthesis of alpha,alpha-
CC trehalose dimycolate (TDM, cord factor). They catalyze the transfer of
CC a mycoloyl residue from one molecule of alpha,alpha-trehalose
CC monomycolate (TMM) to another TMM, leading to the formation of TDM.
CC {ECO:0000269|PubMed:12010501, ECO:0000269|PubMed:3141278,
CC ECO:0000269|PubMed:9162010}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 alpha,alpha'-trehalose 6-mycolate = alpha,alpha'-trehalose
CC 6,6'-bismycolate + alpha,alpha-trehalose; Xref=Rhea:RHEA:23472,
CC ChEBI:CHEBI:16551, ChEBI:CHEBI:18195, ChEBI:CHEBI:18234;
CC EC=2.3.1.122;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycerol + an acyl-CoA = a triacyl-sn-glycerol
CC + CoA; Xref=Rhea:RHEA:10868, ChEBI:CHEBI:17815, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:58342, ChEBI:CHEBI:64615; EC=2.3.1.20;
CC -!- INTERACTION:
CC P9WQP1; PRO_0000009136 [O00602]: FCN1; Xeno; NbExp=3; IntAct=EBI-26878221, EBI-11784425;
CC P9WQP1; Q15485: FCN2; Xeno; NbExp=3; IntAct=EBI-26878221, EBI-7468784;
CC P9WQP1; O75636: FCN3; Xeno; NbExp=4; IntAct=EBI-26878221, EBI-11786958;
CC P9WQP1; PRO_0000017401 [P11226]: MBL2; Xeno; NbExp=2; IntAct=EBI-26878221, EBI-25427940;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene produce normally
CC mycoloylated cell wall components. {ECO:0000269|PubMed:12010501}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the mycobacterial A85 antigen family.
CC {ECO:0000305}.
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DR EMBL; X62398; CAA44269.1; -; Genomic_DNA.
DR EMBL; U38939; AAC44294.1; -; Genomic_DNA.
DR EMBL; GQ150316; ADD50054.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP44652.1; -; Genomic_DNA.
DR PIR; C70516; C70516.
DR RefSeq; NP_216402.1; NC_000962.3.
DR RefSeq; WP_003409456.1; NZ_NVQJ01000013.1.
DR PDB; 1F0N; X-ray; 1.80 A; A=41-325.
DR PDB; 1F0P; X-ray; 1.90 A; A=41-325.
DR PDB; 5TRZ; X-ray; 2.25 A; P/Q=102-110.
DR PDB; 5TS1; X-ray; 2.30 A; P/Q/R/S=101-109.
DR PDBsum; 1F0N; -.
DR PDBsum; 1F0P; -.
DR PDBsum; 5TRZ; -.
DR PDBsum; 5TS1; -.
DR AlphaFoldDB; P9WQP1; -.
DR SMR; P9WQP1; -.
DR IntAct; P9WQP1; 4.
DR STRING; 83332.Rv1886c; -.
DR ESTHER; myctu-a85b; A85-Mycolyl-transferase.
DR MoonProt; P9WQP1; -.
DR PaxDb; 83332-Rv1886c; -.
DR DNASU; 885785; -.
DR GeneID; 45425859; -.
DR GeneID; 885785; -.
DR KEGG; mtu:Rv1886c; -.
DR TubercuList; Rv1886c; -.
DR eggNOG; COG0627; Bacteria.
DR InParanoid; P9WQP1; -.
DR OrthoDB; 4366784at2; -.
DR PhylomeDB; P9WQP1; -.
DR BioCyc; MetaCyc:G185E-6081-MONOMER; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; IDA:CAFA.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; IDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0016747; F:acyltransferase activity, transferring groups other than amino-acyl groups; IDA:MTBBASE.
DR GO; GO:0004144; F:diacylglycerol O-acyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0001968; F:fibronectin binding; IDA:CAFA.
DR GO; GO:0050348; F:trehalose O-mycolyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0035375; F:zymogen binding; IPI:CAFA.
DR GO; GO:0010756; P:positive regulation of plasminogen activation; IDA:CAFA.
DR GO; GO:0040009; P:regulation of growth rate; IMP:UniProtKB.
DR GO; GO:0046677; P:response to antibiotic; IDA:MTBBASE.
DR GO; GO:0052572; P:response to host immune response; IEP:MTBBASE.
DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000801; Esterase-like.
DR PANTHER; PTHR48098:SF1; DIACYLGLYCEROL ACYLTRANSFERASE_MYCOLYLTRANSFERASE AG85A; 1.
DR PANTHER; PTHR48098; ENTEROCHELIN ESTERASE-RELATED; 1.
DR Pfam; PF00756; Esterase; 1.
DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Direct protein sequencing; Disulfide bond;
KW Reference proteome; Secreted; Signal; Transferase.
FT SIGNAL 1..40
FT /evidence="ECO:0000255"
FT CHAIN 41..325
FT /note="Diacylglycerol acyltransferase/mycolyltransferase
FT Ag85B"
FT /id="PRO_0000000222"
FT REGION 98..108
FT /note="Fibronectin-binding"
FT /evidence="ECO:0000250"
FT ACT_SITE 166
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:11254389"
FT ACT_SITE 270
FT /evidence="ECO:0000305|PubMed:11254389"
FT ACT_SITE 302
FT /evidence="ECO:0000305|PubMed:11254389"
FT BINDING 82..83
FT /ligand="substrate"
FT BINDING 166
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11254389"
FT BINDING 194
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11254389"
FT BINDING 272..275
FT /ligand="substrate"
FT BINDING 279
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11254389"
FT BINDING 302..304
FT /ligand="substrate"
FT DISULFID 127..132
FT /evidence="ECO:0000269|PubMed:11254389"
FT STRAND 48..55
FT /evidence="ECO:0007829|PDB:1F0N"
FT TURN 56..59
FT /evidence="ECO:0007829|PDB:1F0N"
FT STRAND 60..67
FT /evidence="ECO:0007829|PDB:1F0N"
FT STRAND 75..79
FT /evidence="ECO:0007829|PDB:1F0N"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:1F0N"
FT HELIX 90..94
FT /evidence="ECO:0007829|PDB:1F0N"
FT HELIX 97..101
FT /evidence="ECO:0007829|PDB:1F0N"
FT STRAND 107..111
FT /evidence="ECO:0007829|PDB:1F0N"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:1F0N"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:1F0N"
FT HELIX 137..142
FT /evidence="ECO:0007829|PDB:1F0N"
FT HELIX 144..153
FT /evidence="ECO:0007829|PDB:1F0N"
FT STRAND 157..165
FT /evidence="ECO:0007829|PDB:1F0N"
FT HELIX 167..178
FT /evidence="ECO:0007829|PDB:1F0N"
FT TURN 180..182
FT /evidence="ECO:0007829|PDB:1F0N"
FT STRAND 183..190
FT /evidence="ECO:0007829|PDB:1F0N"
FT HELIX 200..210
FT /evidence="ECO:0007829|PDB:1F0N"
FT HELIX 216..220
FT /evidence="ECO:0007829|PDB:1F0N"
FT HELIX 227..230
FT /evidence="ECO:0007829|PDB:1F0N"
FT TURN 233..236
FT /evidence="ECO:0007829|PDB:1F0N"
FT HELIX 237..242
FT /evidence="ECO:0007829|PDB:1F0N"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:1F0N"
FT HELIX 264..286
FT /evidence="ECO:0007829|PDB:1F0N"
FT STRAND 291..295
FT /evidence="ECO:0007829|PDB:1F0N"
FT HELIX 304..322
FT /evidence="ECO:0007829|PDB:1F0N"
SQ SEQUENCE 325 AA; 34581 MW; B993B5442FD5567D CRC64;
MTDVSRKIRA WGRRLMIGTA AAVVLPGLVG LAGGAATAGA FSRPGLPVEY LQVPSPSMGR
DIKVQFQSGG NNSPAVYLLD GLRAQDDYNG WDINTPAFEW YYQSGLSIVM PVGGQSSFYS
DWYSPACGKA GCQTYKWETF LTSELPQWLS ANRAVKPTGS AAIGLSMAGS SAMILAAYHP
QQFIYAGSLS ALLDPSQGMG PSLIGLAMGD AGGYKAADMW GPSSDPAWER NDPTQQIPKL
VANNTRLWVY CGNGTPNELG GANIPAEFLE NFVRSSNLKF QDAYNAAGGH NAVFNFPPNG
THSWEYWGAQ LNAMKGDLQS SLGAG
//
