ATAJ_ASPTN
ID ATAJ_ASPTN Reviewed; 410 AA.
AC Q0CS61;
DT 05-JUL-2017, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Dipeptidase ataJ {ECO:0000303|PubMed:23586797};
DE EC=3.4.13.19 {ECO:0000255|PROSITE-ProRule:PRU10073};
DE AltName: Full=Acetylaranotin biosynthesis cluster protein J {ECO:0000303|PubMed:23586797};
GN Name=ataJ {ECO:0000303|PubMed:23586797}; ORFNames=ATEG_03473;
OS Aspergillus terreus (strain NIH 2624 / FGSC A1156).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=341663;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NIH 2624 / FGSC A1156;
RA Birren B.W., Lander E.S., Galagan J.E., Nusbaum C., Devon K., Henn M.,
RA Ma L.-J., Jaffe D.B., Butler J., Alvarez P., Gnerre S., Grabherr M.,
RA Kleber M., Mauceli E.W., Brockman W., Rounsley S., Young S.K., LaButti K.,
RA Pushparaj V., DeCaprio D., Crawford M., Koehrsen M., Engels R.,
RA Montgomery P., Pearson M., Howarth C., Larson L., Luoma S., White J.,
RA Alvarado L., Kodira C.D., Zeng Q., Oleary S., Yandava C., Denning D.W.,
RA Nierman W.C., Milne T., Madden K.;
RT "Annotation of the Aspergillus terreus NIH2624 genome.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=23586797; DOI=10.1021/ja3123653;
RA Guo C.J., Yeh H.H., Chiang Y.M., Sanchez J.F., Chang S.L., Bruno K.S.,
RA Wang C.C.;
RT "Biosynthetic pathway for the epipolythiodioxopiperazine acetylaranotin in
RT Aspergillus terreus revealed by genome-based deletion analysis.";
RL J. Am. Chem. Soc. 135:7205-7213(2013).
RN [3]
RP FUNCTION.
RX PubMed=30096370; DOI=10.1016/j.fgb.2018.08.001;
RA Sun W.W., Romsdahl J., Guo C.J., Wang C.C.C.;
RT "Genome-based deletion analysis in Aspergillus terreus reveals the
RT acetylaranotin bis-thiomethyltransferase gene.";
RL Fungal Genet. Biol. 119:1-6(2018).
CC -!- FUNCTION: Dipeptidase; part of the gene cluster that mediates the
CC biosynthesis of acetylaranotin, a member of the
CC epipolythiodioxopiperazine (ETP) class of toxins characterized by a
CC disulfide-bridged cyclic dipeptide (PubMed:23586797). The first step of
CC acetylaranotin biosynthesis is performed by the NRPS ataP which
CC produces diketopiperazine cyclo-L-Phe-L-Phe via the condensation of 2
CC phenylalanines (L-Phe) (PubMed:23586797). The ataC domain of ataTC then
CC catalyzes the formation of bishydroxylation of cyclo-L-Phe-L-Phe
CC (PubMed:23586797). The glutathione S-transferase domain ataG in ataIMG
CC further catalyzes the conjugation of two glutathiones to the
CC bishydroxylated intermediate (PubMed:23586797). Next, the dipeptidase
CC ataJ removes the Glu residues (PubMed:23586797). The following step is
CC performed by the carbon sulfur lyase domain ataI of ataIMG which may
CC convert the bis-cysteinyl adduct to yield an epidithiol intermediate
CC (PubMed:23586797). The ataT domain from ataTC then catalyzes the
CC oxidation of the free dithiols, followed by a cyclization step
CC catalyzed by the cytochrome P450 ataF (PubMed:23586797). AtaF probably
CC acts as an epoxidase to promote a dual epoxidation formation at C8 and
CC C9 along with C8' and C9', followed by the spontaneous nucleophilic
CC attack of the amide nitrogens N10 and N10' to yield an intermediate
CC with the pyrrolidine partial structure (PubMed:23586797). The final
CC steps of acetylaranotin biosynthesis involve the acetylation and ring
CC rearrangement of an epitetrathiodiketopiperazine intermediate to
CC produce acetylaranotin (PubMed:23586797). AtaH probably catalyzes the
CC acetylation of epitetrathiodiketopiperazine to produce a diacetate and
CC ataY is responsible for the formation of the dihydrooxepin moiety that
CC converts the diacetate intermediate to acetylaranotin via
CC acetylapoaranotin (PubMed:23586797). Both enzymes could function
CC independently in the absence of the other (PubMed:23586797). The
CC acetylaranotin bis-thiomethyltransferase ataS located outside of
CC acetylaranotin gene cluster is the main thiomethyltransferase
CC responsible for converting acetylaranotin and its related intermediates
CC to their methylated forms (PubMed:30096370).
CC {ECO:0000269|PubMed:23586797, ECO:0000269|PubMed:30096370}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an L-aminoacyl-L-amino acid + H2O = 2 an L-alpha-amino acid;
CC Xref=Rhea:RHEA:48940, ChEBI:CHEBI:15377, ChEBI:CHEBI:59869,
CC ChEBI:CHEBI:77460; EC=3.4.13.19; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10073};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10073};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:23586797}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of acetylaranotin and
CC accumulates chemically stable intermediate cyclo-L-phe-L-phe or shunt
CC products such as 2-hydroxy-2'-ene-cyclo-L-Phe-L-Phe and 2-imino-10'-
CC hydroxy-cyclo-L-Phe-L-Phe (PubMed:23586797).
CC {ECO:0000269|PubMed:23586797}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Peptidase M19 family. {ECO:0000255|PROSITE-ProRule:PRU10073}.
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DR EMBL; CH476597; EAU36747.1; -; Genomic_DNA.
DR RefSeq; XP_001212651.1; XM_001212651.1.
DR AlphaFoldDB; Q0CS61; -.
DR SMR; Q0CS61; -.
DR STRING; 341663.Q0CS61; -.
DR MEROPS; M19.013; -.
DR EnsemblFungi; EAU36747; EAU36747; ATEG_03473.
DR GeneID; 4317581; -.
DR VEuPathDB; FungiDB:ATEG_03473; -.
DR eggNOG; KOG4127; Eukaryota.
DR HOGENOM; CLU_031404_4_0_1; -.
DR OMA; EEVQNSC; -.
DR OrthoDB; 1272387at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070573; F:metallodipeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd01301; rDP_like; 1.
DR InterPro; IPR032466; Metal_Hydrolase.
DR InterPro; IPR008257; Pept_M19.
DR PANTHER; PTHR10443; PTHR10443; 1.
DR Pfam; PF01244; Peptidase_M19; 1.
DR SUPFAM; SSF51556; SSF51556; 1.
DR PROSITE; PS51365; RENAL_DIPEPTIDASE_2; 1.
PE 3: Inferred from homology;
KW Dipeptidase; Hydrolase; Metal-binding; Metalloprotease; Protease;
KW Reference proteome; Zinc.
FT CHAIN 1..410
FT /note="Dipeptidase ataJ"
FT /id="PRO_0000440661"
FT REGION 180..200
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 27
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT BINDING 29
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT BINDING 138
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT BINDING 165
FT /ligand="substrate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT BINDING 258
FT /ligand="substrate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT BINDING 318
FT /ligand="substrate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
SQ SEQUENCE 410 AA; 45562 MW; 883B0E7E2CD8078D CRC64;
MTTDLNQNPY LVRAQQLLCR VPLIDGHNDF PFIIRGLYQN NLTRASLNDL PIGQTDISRL
RQGSVGGQFW SAYVPNPVHS DKESDEAYLE CLRQTLQQID VIHRMVSEHP DVFGLAQSAA
DVWKIFRAGR IASLIGIEGL HQIAHSPSAL RMMHKLGVRY ATLCHTKNNR YCDSAVDRHT
SSPWSEYGGQ THDPGDEPSR NVRTGFHSLT LKYLTAVHGR IVDLSHTSEA TQRDAIAISK
APVIFSHSAS SSLTPSPRNV TDEILHQLKR NGGLIMVCFL RDLVNSADDA NTTGSRVVDH
ILYIAETIGY DHVGIGSDFD GMLEGPLGLD DVSRFPELVA DLFRRGVSEE RIEKIVGLNT
LRVMKQVEDV AVREQAEGST GVLCDVVKPI WTAEQRQMLA EQGRTRGLRP
