A85C_MYCTU
ID A85C_MYCTU Reviewed; 340 AA.
AC P9WQN9; L0T2K1; P0A4V4; P31953; P96806;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Diacylglycerol acyltransferase/mycolyltransferase Ag85C;
DE Short=DGAT;
DE EC=2.3.1.122;
DE EC=2.3.1.20;
DE AltName: Full=Acyl-CoA:diacylglycerol acyltransferase;
DE AltName: Full=Antigen 85 complex C;
DE Short=85C;
DE Short=Ag85C;
DE AltName: Full=Fibronectin-binding protein C;
DE Short=Fbps C;
DE Flags: Precursor;
GN Name=fbpC; Synonyms=mpt45; OrderedLocusNames=Rv0129c; ORFNames=MTCI5.03c;
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 [GENOMIC DNA].
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=1715324; DOI=10.1128/iai.59.9.3205-3212.1991;
RA Content J., la Cuvellerie A., de Wit L., Vincent-Levy-Frebault V., Ooms J.,
RA de Bruyn J.;
RT "The genes coding for the antigen 85 complexes of Mycobacterium
RT tuberculosis and Mycobacterium bovis BCG are members of a gene family:
RT cloning, sequence determination, and genomic organization of the gene
RT coding for antigen 85-C of M. tuberculosis.";
RL Infect. Immun. 59:3205-3212(1991).
RN [2]
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 [3]
RP PROTEIN SEQUENCE OF 47-56.
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 [4]
RP FUNCTION IN THE FIBRONECTIN-BINDING.
RX PubMed=1830294; DOI=10.1128/iai.59.8.2712-2718.1991;
RA Abou-Zeid C., Garbe T., Lathigra R., Wiker H.G., Harboe M., Rook G.A.,
RA Young D.B.;
RT "Genetic and immunological analysis of Mycobacterium tuberculosis
RT fibronectin-binding proteins.";
RL Infect. Immun. 59:2712-2718(1991).
RN [5]
RP FUNCTION AS A MYCOLYLTRANSFERASE, MUTAGENESIS OF SER-170, ACTIVITY
RP REGULATION, 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 [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=10200974; DOI=10.1046/j.1365-2958.1999.01310.x;
RA Jackson M., Raynaud C., Laneelle M.A., Guilhot C., Laurent-Winter C.,
RA Ensergueix D., Gicquel B., Daffe M.;
RT "Inactivation of the antigen 85C gene profoundly affects the mycolate
RT content and alters the permeability of the Mycobacterium tuberculosis cell
RT envelope.";
RL Mol. Microbiol. 31:1573-1587(1999).
RN [7]
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 [8]
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).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 47-328 IN COMPLEX WITH SUBSTRATE
RP ANALOGS, ACTIVE SITE, REACTION MECHANISM, AND SUBUNIT.
RX PubMed=10655617; DOI=10.1038/72413;
RA Ronning D.R., Klabunde T., Besra G.S., Vissa V.D., Belisle J.T.,
RA Sacchettini J.C.;
RT "Crystal structure of the secreted form of antigen 85C reveals potential
RT targets for mycobacterial drugs and vaccines.";
RL Nat. Struct. Biol. 7:141-146(2000).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) OF 47-340 IN COMPLEX WITH SUBSTRATE
RP ANALOG, AND SUBUNIT.
RX PubMed=15192106; DOI=10.1074/jbc.m400811200;
RA Ronning D.R., Vissa V., Besra G.S., Belisle J.T., Sacchettini J.C.;
RT "Mycobacterium tuberculosis antigen 85A and 85C structures confirm binding
RT orientation and conserved substrate specificity.";
RL J. Biol. Chem. 279:36771-36777(2004).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 47-340, AND SUBUNIT.
RX PubMed=19668859; DOI=10.1039/b902284h;
RA Sanki A.K., Boucau J., Umesiri F.E., Ronning D.R., Sucheck S.J.;
RT "Design, synthesis and biological evaluation of sugar-derived esters,
RT alpha-ketoesters and alpha-ketoamides as inhibitors for Mycobacterium
RT tuberculosis antigen 85C.";
RL Mol. Biosyst. 5:945-956(2009).
CC -!- FUNCTION: The antigen 85 proteins (FbpA, FbpB, FbpC) are responsible
CC for the high affinity of mycobacteria to 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:1830294, ECO:0000269|PubMed:9162010}.
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 -!- 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 -!- ACTIVITY REGULATION: Inhibited by 6-azido-6-deoxy-alpha,alpha-trehalose
CC (ADT). {ECO:0000269|PubMed:9162010}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10655617,
CC ECO:0000269|PubMed:15192106, ECO:0000269|PubMed:19668859}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene transfer 40% fewer
CC mycolates to the cell wall with no change in the types of mycolates
CC esterified to arabinogalactan or in the composition of non-covalently
CC linked mycolates. As a consequence, the diffusion of hydrophobic
CC chenodeoxycholate and of hydrophilic glycerol through the cell envelope
CC occurs much more rapidly in mutant cells than in wild-type.
CC {ECO:0000269|PubMed:10200974}.
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; X57229; CAA40506.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP42854.1; -; Genomic_DNA.
DR PIR; D70615; D70615.
DR RefSeq; WP_003400908.1; NZ_NVQJ01000001.1.
DR RefSeq; YP_177694.1; NC_000962.3.
DR PDB; 1DQY; X-ray; 1.83 A; A=47-328.
DR PDB; 1DQZ; X-ray; 1.50 A; A/B=49-328.
DR PDB; 1VA5; X-ray; 2.02 A; A/B=47-340.
DR PDB; 3HRH; X-ray; 2.30 A; A/B=47-340.
DR PDB; 4MQL; X-ray; 1.30 A; A=46-340.
DR PDB; 4MQM; X-ray; 1.35 A; A=46-340.
DR PDB; 4QDO; X-ray; 1.90 A; A=46-340.
DR PDB; 4QDT; X-ray; 1.50 A; A=46-340.
DR PDB; 4QDU; X-ray; 1.40 A; A=46-340.
DR PDB; 4QDX; X-ray; 1.50 A; A=46-340.
DR PDB; 4QDZ; X-ray; 1.88 A; A=46-340.
DR PDB; 4QE3; X-ray; 1.35 A; A=46-340.
DR PDB; 4QEK; X-ray; 1.30 A; A=46-340.
DR PDB; 5KWI; X-ray; 1.30 A; A=47-340.
DR PDB; 5KWJ; X-ray; 2.01 A; A/B=47-340.
DR PDB; 5OCJ; X-ray; 1.80 A; A/B=47-340.
DR PDBsum; 1DQY; -.
DR PDBsum; 1DQZ; -.
DR PDBsum; 1VA5; -.
DR PDBsum; 3HRH; -.
DR PDBsum; 4MQL; -.
DR PDBsum; 4MQM; -.
DR PDBsum; 4QDO; -.
DR PDBsum; 4QDT; -.
DR PDBsum; 4QDU; -.
DR PDBsum; 4QDX; -.
DR PDBsum; 4QDZ; -.
DR PDBsum; 4QE3; -.
DR PDBsum; 4QEK; -.
DR PDBsum; 5KWI; -.
DR PDBsum; 5KWJ; -.
DR PDBsum; 5OCJ; -.
DR AlphaFoldDB; P9WQN9; -.
DR SMR; P9WQN9; -.
DR STRING; 83332.Rv0129c; -.
DR BindingDB; P9WQN9; -.
DR ChEMBL; CHEMBL4624; -.
DR DrugBank; DB08558; 2-HYDROXYMETHYL-6-OCTYLSULFANYL-TETRAHYDRO-PYRAN-3,4,5-TRIOL.
DR DrugBank; DB02811; Diethyl phosphonate.
DR ESTHER; myctu-a85c; A85-Mycolyl-transferase.
DR MoonProt; P9WQN9; -.
DR PaxDb; P9WQN9; -.
DR DNASU; 886885; -.
DR GeneID; 45424095; -.
DR GeneID; 886885; -.
DR KEGG; mtu:Rv0129c; -.
DR TubercuList; Rv0129c; -.
DR eggNOG; COG0627; Bacteria.
DR OMA; WNQQLMA; -.
DR PhylomeDB; P9WQN9; -.
DR BioCyc; MetaCyc:G185E-4246-MON; -.
DR BRENDA; 2.3.1.122; 3445.
DR PRO; PR:P9WQN9; -.
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: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:0050348; F:trehalose O-mycolyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0035375; F:zymogen binding; IPI:CAFA.
DR GO; GO:0009247; P:glycolipid biosynthetic process; IDA:MTBBASE.
DR GO; GO:0006869; P:lipid transport; IMP:MTBBASE.
DR GO; GO:0071769; P:mycolate cell wall layer assembly; IDA:MTBBASE.
DR GO; GO:0046677; P:response to antibiotic; IEP:MTBBASE.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000801; Esterase-like.
DR Pfam; PF00756; Esterase; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Direct protein sequencing;
KW Reference proteome; Secreted; Signal; Transferase.
FT SIGNAL 1..45
FT /evidence="ECO:0000255"
FT CHAIN 46..340
FT /note="Diacylglycerol acyltransferase/mycolyltransferase
FT Ag85C"
FT /id="PRO_0000000226"
FT REGION 102..112
FT /note="Fibronectin-binding"
FT ACT_SITE 170
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:10655617"
FT ACT_SITE 274
FT /evidence="ECO:0000269|PubMed:10655617"
FT ACT_SITE 306
FT /evidence="ECO:0000269|PubMed:10655617"
FT BINDING 86..87
FT /ligand="substrate"
FT BINDING 170
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 198
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 276..279
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 283
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 306..308
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MUTAGEN 170
FT /note="S->A: Do not form alpha,alpha-trehalose dimycolate
FT (TDM, cord factor) and alpha,alpha-trehalose monomycolate
FT (TMM)."
FT /evidence="ECO:0000269|PubMed:9162010"
FT CONFLICT 21
FT /note="L -> V (in Ref. 1; CAA40506)"
FT /evidence="ECO:0000305"
FT STRAND 54..61
FT /evidence="ECO:0007829|PDB:4QEK"
FT TURN 62..65
FT /evidence="ECO:0007829|PDB:4QEK"
FT STRAND 66..73
FT /evidence="ECO:0007829|PDB:4QEK"
FT STRAND 75..82
FT /evidence="ECO:0007829|PDB:4QEK"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:4QEK"
FT HELIX 94..98
FT /evidence="ECO:0007829|PDB:4QEK"
FT HELIX 101..105
FT /evidence="ECO:0007829|PDB:4QEK"
FT STRAND 111..115
FT /evidence="ECO:0007829|PDB:4QEK"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:4QEK"
FT TURN 131..134
FT /evidence="ECO:0007829|PDB:4QEK"
FT HELIX 141..146
FT /evidence="ECO:0007829|PDB:4QEK"
FT HELIX 148..157
FT /evidence="ECO:0007829|PDB:4QEK"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:4QEK"
FT STRAND 165..169
FT /evidence="ECO:0007829|PDB:4QEK"
FT HELIX 172..182
FT /evidence="ECO:0007829|PDB:4QEK"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:4QEK"
FT STRAND 188..194
FT /evidence="ECO:0007829|PDB:4QEK"
FT HELIX 204..214
FT /evidence="ECO:0007829|PDB:4QEK"
FT TURN 215..217
FT /evidence="ECO:0007829|PDB:4QDX"
FT HELIX 220..224
FT /evidence="ECO:0007829|PDB:4QEK"
FT HELIX 230..234
FT /evidence="ECO:0007829|PDB:4QEK"
FT TURN 237..240
FT /evidence="ECO:0007829|PDB:4QEK"
FT HELIX 241..246
FT /evidence="ECO:0007829|PDB:4QEK"
FT STRAND 250..254
FT /evidence="ECO:0007829|PDB:4QEK"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:4QEK"
FT HELIX 272..290
FT /evidence="ECO:0007829|PDB:4QEK"
FT STRAND 295..299
FT /evidence="ECO:0007829|PDB:4QEK"
FT STRAND 305..307
FT /evidence="ECO:0007829|PDB:5KWI"
FT HELIX 308..317
FT /evidence="ECO:0007829|PDB:4QEK"
FT HELIX 319..326
FT /evidence="ECO:0007829|PDB:4QEK"
SQ SEQUENCE 340 AA; 36771 MW; 2D868C438D697988 CRC64;
MTFFEQVRRL RSAATTLPRR LAIAAMGAVL VYGLVGTFGG PATAGAFSRP GLPVEYLQVP
SASMGRDIKV QFQGGGPHAV YLLDGLRAQD DYNGWDINTP AFEEYYQSGL SVIMPVGGQS
SFYTDWYQPS QSNGQNYTYK WETFLTREMP AWLQANKGVS PTGNAAVGLS MSGGSALILA
AYYPQQFPYA ASLSGFLNPS EGWWPTLIGL AMNDSGGYNA NSMWGPSSDP AWKRNDPMVQ
IPRLVANNTR IWVYCGNGTP SDLGGDNIPA KFLEGLTLRT NQTFRDTYAA DGGRNGVFNF
PPNGTHSWPY WNEQLVAMKA DIQHVLNGAT PPAAPAAPAA
