ACLD_ASPOR
ID ACLD_ASPOR Reviewed; 314 AA.
AC Q2UPB5;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Thioredoxin reductase aclD {ECO:0000303|PubMed:25302411};
DE EC=1.8.1.- {ECO:0000305|PubMed:25302411};
DE AltName: Full=Aspirochlorine biosynthesis protein D {ECO:0000303|PubMed:25302411};
GN Name=aclD {ECO:0000303|PubMed:25302411}; ORFNames=AO090001000037;
OS Aspergillus oryzae (strain ATCC 42149 / RIB 40) (Yellow koji mold).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=510516;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 42149 / RIB 40;
RX PubMed=16372010; DOI=10.1038/nature04300;
RA Machida M., Asai K., Sano M., Tanaka T., Kumagai T., Terai G., Kusumoto K.,
RA Arima T., Akita O., Kashiwagi Y., Abe K., Gomi K., Horiuchi H.,
RA Kitamoto K., Kobayashi T., Takeuchi M., Denning D.W., Galagan J.E.,
RA Nierman W.C., Yu J., Archer D.B., Bennett J.W., Bhatnagar D.,
RA Cleveland T.E., Fedorova N.D., Gotoh O., Horikawa H., Hosoyama A.,
RA Ichinomiya M., Igarashi R., Iwashita K., Juvvadi P.R., Kato M., Kato Y.,
RA Kin T., Kokubun A., Maeda H., Maeyama N., Maruyama J., Nagasaki H.,
RA Nakajima T., Oda K., Okada K., Paulsen I., Sakamoto K., Sawano T.,
RA Takahashi M., Takase K., Terabayashi Y., Wortman J.R., Yamada O.,
RA Yamagata Y., Anazawa H., Hata Y., Koide Y., Komori T., Koyama Y.,
RA Minetoki T., Suharnan S., Tanaka A., Isono K., Kuhara S., Ogasawara N.,
RA Kikuchi H.;
RT "Genome sequencing and analysis of Aspergillus oryzae.";
RL Nature 438:1157-1161(2005).
RN [2]
RP FUNCTION, AND PATHWAY.
RX PubMed=25302411; DOI=10.1002/anie.201407624;
RA Chankhamjon P., Boettger-Schmidt D., Scherlach K., Urbansky B., Lackner G.,
RA Kalb D., Dahse H.M., Hoffmeister D., Hertweck C.;
RT "Biosynthesis of the halogenated mycotoxin aspirochlorine in koji mold
RT involves a cryptic amino acid conversion.";
RL Angew. Chem. Int. Ed. 53:13409-13413(2014).
CC -!- FUNCTION: Thioredoxin reductase; part of the gene cluster that mediates
CC the biosynthesis of aspirochlorine (or antibiotic A30641), an unusual
CC halogenated spiro compound with distinctive antifungal properties due
CC to selective inhibition of protein biosynthesis, and which is also
CC active against bacteria, viruses, and murine tumor cells
CC (PubMed:25302411). The non-ribosomal peptide synthetase (NRPS) aclP is
CC responsible the formation of the diketopiperazine (DKP) core from the
CC condensation of 2 phenylalanine residues (PubMed:25302411). One Phe
CC residue is tailored into chlorotyrosine by hydroxylation and
CC chlorination, whereas the second Phe undergoes an unprecedented C-C
CC bond cleavage to be converted into glycine (PubMed:25302411). After
CC formation of the DKP, sulfur is incorporated into the DKP by
CC conjugation with glutathione by aclG, followed by its stepwise
CC degradation to the thiol by aclI, aclJ and aclK, and the dithiol
CC oxidation by aclT (PubMed:25302411). In addition, oxygenases (aclB,
CC aclC, aclL and aclO) and O-methyltransferases (aclM and aclU) act as
CC tailoring enzymes to produce the intermediate dechloroaspirochlorine
CC (PubMed:25302411). Ultimately, chlorination of dechloroaspirochlorine
CC by the halogenase aclH is the last step in the aspirochlorine pathway
CC (PubMed:25302411). {ECO:0000269|PubMed:25302411}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:E9RAH5};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:E9RAH5};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:25302411}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:E9RAH5}.
CC -!- SIMILARITY: Belongs to the class-II pyridine nucleotide-disulfide
CC oxidoreductase family. {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; AP007154; BAE56600.1; -; Genomic_DNA.
DR RefSeq; XP_001818602.1; XM_001818550.2.
DR AlphaFoldDB; Q2UPB5; -.
DR SMR; Q2UPB5; -.
DR EnsemblFungi; BAE56600; BAE56600; AO090001000037.
DR GeneID; 5990573; -.
DR KEGG; aor:AO090001000037; -.
DR VEuPathDB; FungiDB:AO090001000037; -.
DR HOGENOM; CLU_031864_5_0_1; -.
DR OMA; ALMLPDW; -.
DR Proteomes; UP000006564; Chromosome 2.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 3: Inferred from homology;
KW Disulfide bond; FAD; Flavoprotein; Oxidoreductase; Reference proteome.
FT CHAIN 1..314
FT /note="Thioredoxin reductase aclD"
FT /id="PRO_0000441209"
FT BINDING 13..16
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
FT BINDING 35..40
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
FT BINDING 47
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
FT BINDING 112
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
FT BINDING 281
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
FT BINDING 288..289
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
FT DISULFID 136..139
FT /note="Redox-active"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
SQ SEQUENCE 314 AA; 34066 MW; 7BBAE33C81F2C4DA CRC64;
MAAPLFDCLI VGGGPAGLAA ALGLCRAIRT AVVFDSKSYR NPTEHMHNVS TWDHANPHDY
RLAARKELTE GRYNTVTLAD VALRKIWKLD SGEFEATDAV GKVWKGRKLI LATGVKDEIP
ELPGYADCWP KSIYHCLFCH GFEERGAPSV GVLAIGPVAN PKPAEHLSRL AHNLAKTVTI
YTNGNEELAA QLRPSIEKDQ WLTLDNRVIK QLHKTDGIPV RVELDDGTTK EEGFLVHAMK
TTPRLDFEHN LNLELSAQGT EFVASPPFSE TTTPGCFATG DCGMAIKAAS MSMSNGSLAA
VGVVSQLAFD EKAK
