ADAB_ASPNC
ID ADAB_ASPNC Reviewed; 317 AA.
AC A2QX23;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=Lactamase-like protein adaB {ECO:0000303|PubMed:21866960};
DE EC=3.1.-.- {ECO:0000269|PubMed:21866960};
DE AltName: Full=2-acetyl-2-decarboxamidoanthrotainin biosynthesis cluster protein B {ECO:0000303|PubMed:21866960};
GN Name=adaB {ECO:0000303|PubMed:21866960}; ORFNames=An11g07320;
OS Aspergillus niger (strain CBS 513.88 / FGSC A1513).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=425011;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CBS 513.88 / FGSC A1513 / ATCC MYA-4892;
RX PubMed=17259976; DOI=10.1038/nbt1282;
RA Pel H.J., de Winde J.H., Archer D.B., Dyer P.S., Hofmann G., Schaap P.J.,
RA Turner G., de Vries R.P., Albang R., Albermann K., Andersen M.R.,
RA Bendtsen J.D., Benen J.A.E., van den Berg M., Breestraat S., Caddick M.X.,
RA Contreras R., Cornell M., Coutinho P.M., Danchin E.G.J., Debets A.J.M.,
RA Dekker P., van Dijck P.W.M., van Dijk A., Dijkhuizen L., Driessen A.J.M.,
RA d'Enfert C., Geysens S., Goosen C., Groot G.S.P., de Groot P.W.J.,
RA Guillemette T., Henrissat B., Herweijer M., van den Hombergh J.P.T.W.,
RA van den Hondel C.A.M.J.J., van der Heijden R.T.J.M., van der Kaaij R.M.,
RA Klis F.M., Kools H.J., Kubicek C.P., van Kuyk P.A., Lauber J., Lu X.,
RA van der Maarel M.J.E.C., Meulenberg R., Menke H., Mortimer M.A.,
RA Nielsen J., Oliver S.G., Olsthoorn M., Pal K., van Peij N.N.M.E.,
RA Ram A.F.J., Rinas U., Roubos J.A., Sagt C.M.J., Schmoll M., Sun J.,
RA Ussery D., Varga J., Vervecken W., van de Vondervoort P.J.J., Wedler H.,
RA Woesten H.A.B., Zeng A.-P., van Ooyen A.J.J., Visser J., Stam H.;
RT "Genome sequencing and analysis of the versatile cell factory Aspergillus
RT niger CBS 513.88.";
RL Nat. Biotechnol. 25:221-231(2007).
RN [2]
RP IDENTIFICATION, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=21866960; DOI=10.1021/ja206906d;
RA Li Y., Chooi Y.H., Sheng Y., Valentine J.S., Tang Y.;
RT "Comparative characterization of fungal anthracenone and naphthacenedione
RT biosynthetic pathways reveals an alpha-hydroxylation-dependent Claisen-like
RT cyclization catalyzed by a dimanganese thioesterase.";
RL J. Am. Chem. Soc. 133:15773-15785(2011).
CC -!- FUNCTION: Lactamase-like protein; part of the gene cluster that
CC mediates the biosynthesis of the linear tetracyclic TAN-1612
CC neuropeptide Y receptor antagonist (PubMed:21866960). The decaketide
CC backbone of TAN-1612 is synthesized by the non-reducing polyketide
CC synthase adaA via condensation of one acetyl-CoA starter unit with 9
CC malonyl-CoA units. The FAD-dependent monooxygenase adaC then performs
CC hydroxylation at C2 while the polaketide chain is still attached to the
CC NRPKS adaA (PubMed:21866960). The alpha-hydroxylation step at C2
CC appears to be crucial for the following C18-C1 Claisen cyclization and
CC release of the C9-hydroxyl version of TAN-1612 from the NRPKS adaA, two
CC steps performed by the lactamase-like protein adaB (PubMed:21866960).
CC Finally, the O-methyltransferase adaD performs the C9 O-methylation to
CC complete the biosynthesis of TAN-1612 (PubMed:21866960).
CC {ECO:0000269|PubMed:21866960}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-(2,4-dioxopentyl)-2,3,6,8,9-pentahydroxy-1-oxo-1,2,3,4-
CC tetrahydroanthracene-2-carboxyl-[ACP] = 2-acetyl-3,4a,8,10,11,12a-
CC hexahydroxy-1,4,4a,5,12,12a-hexahydrotetracene-1,12-dione + H(+) +
CC holo-[ACP]; Xref=Rhea:RHEA:64096, Rhea:RHEA-COMP:9685, Rhea:RHEA-
CC COMP:16520, ChEBI:CHEBI:15378, ChEBI:CHEBI:64479, ChEBI:CHEBI:146218,
CC ChEBI:CHEBI:149688; Evidence={ECO:0000269|PubMed:21866960};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64097;
CC Evidence={ECO:0000269|PubMed:21866960};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q988B9};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:Q988B9};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:21866960}.
CC -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily.
CC {ECO:0000305}.
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DR EMBL; AM270243; CAK40779.1; -; Genomic_DNA.
DR RefSeq; XP_001394706.1; XM_001394669.1.
DR AlphaFoldDB; A2QX23; -.
DR SMR; A2QX23; -.
DR PaxDb; A2QX23; -.
DR EnsemblFungi; CAK40779; CAK40779; An11g07320.
DR GeneID; 4984952; -.
DR KEGG; ang:ANI_1_2244094; -.
DR VEuPathDB; FungiDB:An11g07320; -.
DR HOGENOM; CLU_048478_1_0_1; -.
DR Proteomes; UP000006706; Chromosome 7R.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.60.15.10; -; 1.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR Pfam; PF00753; Lactamase_B; 1.
DR SMART; SM00849; Lactamase_B; 1.
DR SUPFAM; SSF56281; SSF56281; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..317
FT /note="Lactamase-like protein adaB"
FT /id="PRO_0000446350"
FT ACT_SITE 101
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255"
FT BINDING 97
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 101
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 102
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
SQ SEQUENCE 317 AA; 35195 MW; 04C16EB02BD5431E CRC64;
MAFRIPFAQS FWQEYLSGQE ANLPRLPEVE QVTETVMRIL GGNPGRMQLQ GTNTYLVGTG
KFRILIDTGQ GEASWIEALT KQLEANGLEI SHVLLTHWHG DHTGGVPDLI TYNPELSSRV
YKNTPDLGQQ AIHDGQKFHV EGATIRAVFT PGHAFDHMCF LLEEENALFT GDNVLGHGYS
VVEDLGTYMT SLTRMADLNC ALGYPAHGTR IEDLPAKMKE YIQHKESRMR QVLAALERSR
ARMTATGGGR RAGALTFPEL INSMYGGIPD EIEQALTPFL SQVLWKLAED RKVGFEGEPS
QRRWFAVGPP AATAVRL
