NSCB_ASPFU
ID NSCB_ASPFU Reviewed; 330 AA.
AC Q4WA58;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Lactamase-like protein nscB {ECO:0000303|PubMed:23368997};
DE EC=3.1.-.- {ECO:0000305|PubMed:23368997};
DE AltName: Full=Neosartoricin biosynthesis protein B {ECO:0000303|PubMed:23368997};
GN Name=nscB {ECO:0000303|PubMed:23368997}; ORFNames=AFUA_7G00120;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP FUNCTION.
RX PubMed=23758576; DOI=10.1021/sb400048b;
RA Yin W.B., Chooi Y.H., Smith A.R., Cacho R.A., Hu Y., White T.C., Tang Y.;
RT "Discovery of cryptic polyketide metabolites from dermatophytes using
RT heterologous expression in Aspergillus nidulans.";
RL ACS Synth. Biol. 2:629-634(2013).
RN [3]
RP FUNCTION.
RX PubMed=23368997; DOI=10.1021/ol303435y;
RA Chooi Y.H., Fang J., Liu H., Filler S.G., Wang P., Tang Y.;
RT "Genome mining of a prenylated and immunosuppressive polyketide from
RT pathogenic fungi.";
RL Org. Lett. 15:780-783(2013).
CC -!- FUNCTION: Lactamase-like protein; part of the gene cluster that
CC mediates the biosynthesis of neosartoricin, a prenylated anthracenone
CC that exhibits T-cell antiproliferative activity, suggestive of a
CC physiological role as an immunosuppressive agent (PubMed:23758576,
CC PubMed:23368997). The non-reducing polyketide synthase nscA probably
CC synthesizes and cyclizes the decaketide backbone (PubMed:23368997). The
CC hydrolase nscB then mediates the product release through hydrolysis
CC followed by spontaneous decarboxylation (PubMed:23368997). The
CC prenyltransferase nscD catalyzes the addition of the dimethylallyl
CC group to the aromatic C5 (PubMed:23368997). The FAD-dependent
CC monooxygenase nscC is then responsible for the stereospecific
CC hydroxylation at C2 (PubMed:23368997). There is no gene encoding O-
CC acetyltransferase in the nsc gene cluster; thus, the last step of 2-O-
CC acetylation leading to neosartoricin may be catalyzed by an
CC unidentified O-acetyltransferase (PubMed:23368997).
CC {ECO:0000305|PubMed:23368997, ECO:0000305|PubMed:23758576}.
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:0000305|PubMed:23368997}.
CC -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily.
CC {ECO:0000305}.
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DR EMBL; AAHF01000015; EAL84878.1; -; Genomic_DNA.
DR RefSeq; XP_746916.1; XM_741823.1.
DR AlphaFoldDB; Q4WA58; -.
DR SMR; Q4WA58; -.
DR STRING; 746128.CADAFUBP00008425; -.
DR EnsemblFungi; EAL84878; EAL84878; AFUA_7G00120.
DR GeneID; 3504313; -.
DR KEGG; afm:AFUA_7G00120; -.
DR VEuPathDB; FungiDB:Afu7g00120; -.
DR eggNOG; KOG0813; Eukaryota.
DR HOGENOM; CLU_048478_1_0_1; -.
DR InParanoid; Q4WA58; -.
DR OMA; PAKLIVW; -.
DR OrthoDB; 576967at2759; -.
DR Proteomes; UP000002530; Chromosome 7.
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; IBA:GO_Central.
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 3: Inferred from homology;
KW Hydrolase; Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..330
FT /note="Lactamase-like protein nscB"
FT /id="PRO_0000437896"
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 330 AA; 36492 MW; 1090D83924373BC5 CRC64;
MALRMPFNQA FWEEYLSGQD ATLPSLPDTS TLTSRVIRIL GGNPGAMHLQ GTNTYLVGTG
PSRILIDTGQ GLPIWLSRIV GVLQSNNISI SHILLTHWHG DHTGGVPDLI SYNPTLAEHV
YKNLPDLGQK PIEDGQIFAV EGATVRAVFT PGHSVDHMCF LLEEENALFT GDNVLGHGFS
VAPDLGRYME SLELMAKLGC VIGYPAHGAV IDDLPSKLEE YIRHKEMRVQ GILSVLVKER
ERVEGERGKE GRRKGGMTLH EIARAMFGTV PDEVIDQAMA PFLMQALWKL TEDGKVGFEP
GDPVKRKWFA VARRKTRPSI RRQHGSVTSR
