ATRA_TAPPA
ID ATRA_TAPPA Reviewed; 957 AA.
AC B7STY1;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 1.
DT 03-AUG-2022, entry version 34.
DE RecName: Full=Atromentin synthetase {ECO:0000303|PubMed:18805498};
DE EC=2.3.1.- {ECO:0000269|PubMed:18805498};
DE AltName: Full=Atromentin biosynthesis protein A {ECO:0000305};
DE AltName: Full=Nonribosomal peptide synthase atrA {ECO:0000305};
GN Name=atrA {ECO:0000303|PubMed:18805498};
OS Tapinella panuoides (Oyster rollrim mushroom) (Paxillus panuoides).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Boletales; Tapinellineae; Tapinellaceae; Tapinella.
OX NCBI_TaxID=80604;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=18805498; DOI=10.1016/j.fgb.2008.08.009;
RA Schneider P., Bouhired S., Hoffmeister D.;
RT "Characterization of the atromentin biosynthesis genes and enzymes in the
RT homobasidiomycete Tapinella panuoides.";
RL Fungal Genet. Biol. 45:1487-1496(2008).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=5862512; DOI=10.1002/jps.2600540714;
RA Khanna J.M., Malone M.H., Euler K.L., Brady L.R.;
RT "Atromentin, anticoagulant from Hydnellum diabolus.";
RL J. Pharm. Sci. 54:1016-1020(1965).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=6541963; DOI=10.1139/m84-166;
RA Brewer D., Jen W.C., Jones G.A., Taylor A.;
RT "The antibacterial activity of some naturally occurring 2,5-dihydroxy-1,4-
RT benzoquinones.";
RL Can. J. Microbiol. 30:1068-1072(1984).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=17323650; DOI=10.1038/ja.2006.108;
RA Zheng C.J., Sohn M.J., Kim W.G.;
RT "Atromentin and leucomelone, the first inhibitors specific to enoyl-ACP
RT reductase (FabK) of Streptococcus pneumoniae.";
RL J. Antibiot. 59:808-812(2006).
RN [5]
RP BIOTECHNOLOGY.
RX PubMed=19809251; DOI=10.4014/jmb.0811.617;
RA Kim J.H., Lee C.H.;
RT "Atromentin-induced apoptosis in human leukemia U937 cells.";
RL J. Microbiol. Biotechnol. 19:946-950(2009).
CC -!- FUNCTION: The L-tyrosine:2-oxoglutarate aminotransferase atrD and the
CC atromentin synthetase atrA catalyze consecutive steps to turn over L-
CC tyrosine into atromentin, which represents the generic precursor
CC molecule for the entire terphenylquinone and pulvinic acid family of
CC pigments, which are widely distributed secondary metabolites in
CC homobasidiomycetes (PubMed:18805498). The first step is catalyzed by
CC atrD which converts L-tyrosine in to 4-hydroxyphenylpyruvate (4-HPP)
CC (PubMed:18805498). Adenylation of two 4-HPP monomers by the atrA
CC adenylation (A) domain, ester bond formation between monomers and atrA,
CC and symmetric C-C-bond formation between two monomers by atrA leads to
CC atromentin (PubMed:18805498). {ECO:0000269|PubMed:18805498}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.37 uM for 4-hydroxyphenylpyruvic acid
CC {ECO:0000269|PubMed:18805498};
CC KM=590 uM for 2-oxoglutarate {ECO:0000269|PubMed:18805498};
CC pH dependence:
CC Optimum pH is 6.5. {ECO:0000269|PubMed:18805498};
CC Temperature dependence:
CC Optimum temperature is 25 degrees Celsius.
CC {ECO:0000269|PubMed:18805498};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:18805498}.
CC -!- BIOTECHNOLOGY: Atromentin has been shown to induce caspase-3 and poly
CC (ADP-ribose) polymerase (PARP) in human leukemia U937 cells
CC (PubMed:19809251). It has also anticoagulant activity (PubMed:5862512).
CC Moreover, atromentin has antimicrobial activity (PubMed:6541963). It
CC acts especially as an inhibitor of FabK, the enoyl-acyl carrier protein
CC (ACP) reductase of S.pneumoniae (PubMed:17323650).
CC {ECO:0000269|PubMed:17323650, ECO:0000269|PubMed:19809251,
CC ECO:0000269|PubMed:5862512, ECO:0000269|PubMed:6541963}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; EU711405; ACH90386.1; -; Genomic_DNA.
DR AlphaFoldDB; B7STY1; -.
DR SMR; B7STY1; -.
DR BioCyc; MetaCyc:MON-18722; -.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0044249; P:cellular biosynthetic process; IEA:UniProt.
DR GO; GO:1901576; P:organic substance biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR036736; ACP-like_sf.
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; IPR020802; PKS_thioesterase.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR001031; Thioesterase.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00824; PKS_TE; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..957
FT /note="Atromentin synthetase"
FT /id="PRO_0000437678"
FT DOMAIN 596..674
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 59..464
FT /note="Adenylation (A) domain"
FT /evidence="ECO:0000255"
FT REGION 601..671
FT /note="Thiolation and peptide carrier (T) domain"
FT /evidence="ECO:0000255"
FT REGION 697..947
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000255"
FT MOD_RES 633
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 957 AA; 105038 MW; 473D0BBFF8F3B527 CRC64;
MAPTAVFSNP ATNPVANLKA SVKTAEGVPA TLNDLLLQAT EMYPSHELSF ITSSAHDSSV
QARTFQDFNQ RVRNLASALA AWKKPAGEVV VVYLTEHEDN MSAVWACLLA GLVPCLQPAL
SAQQEHKEGH IAHIRKLFGS ATWLTNDAGA MQLDTIKGLD VHLFSDLLAS AEKSSVAANY
VARQSQPDDE AILFLTSGST GFSKAVVHTH RTIINACIAK GANYRLTPQT NILNWVGFDH
VAGSLEMHIA PLLYGCSQLH VHASAILSDP LLLLRLIDER SIDIAFAPNF LLAKMVRDLE
KRTDLHGKFD LSSLRRMNSG GEAVVSKTAV AFVQLLKKLG RNPSKVSFKV AAGFGMTETC
AGCIYDVVDL AENSPKHEFL ALGAPVHGCE MRIVDPEDGA TPRSDGQPGE LQVRGPMIFV
RYYNNPEATK SSFVEGGWYR TGDIGIIENG NMRLSGRIKD TVIVHGVSYG IPELETYLQT
VQGVTHSFLA AAPYRAPGQE TEGFVVFYAP TFDLQGDDAS KKLSETHRAI KDVSVKMMTL
PPQHIVPIPM DQMEKTTLGK LSRARLLSQF VQGALAKHVA RAEELISMAR GASFVTPSTD
DEKALAAIYA GIFNLQSNEV SARDNFFELG GTSIDVIRLK REGEAHFGLS EIPIIQILKN
PIVSDLAKYV NGLVNNDASA NEYDPIVPLQ LSGDKTPIFF VHPGVGEVLI FVNLAKYFQN
ERPFYAFRAR GFEPGHPFFG SMDEMVTSYA NAMKKTQPKG PYAIAGYSYG GVVAFEVAKR
LESMGEEVKF VGLINIPPHI ADRMHEIDWT GGMLNLAYFL SLVTKQDATD LHPKLKTMTK
EEQLEVVWKL APPERVTELQ LTPGKLDHWV SIAGSLIECG KSYNPGGNVS AVDVFYAIPL
KGSKEDWLNK QLKPWSQFSR GEPQFIDVPG QHYTLMDFDH VPQFQKIFRG RLEARGL
