FSQD_ASPFU
ID FSQD_ASPFU Reviewed; 574 AA.
AC Q4WD45;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=ATP-grasp enzyme fsqD {ECO:0000303|PubMed:27065235};
DE EC=6.3.2.- {ECO:0000305|PubMed:27065235};
DE AltName: Full=Fumipyrrole biosynthesis protein C {ECO:0000303|PubMed:25582336};
DE AltName: Full=Fumisoquins biosynthesis protein D {ECO:0000303|PubMed:27065235};
GN Name=fsqD {ECO:0000303|PubMed:27065235};
GN Synonyms=fmpC {ECO:0000303|PubMed:25582336}; ORFNames=AFUA_6G03460;
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, AND INDUCTION.
RX PubMed=25582336; DOI=10.1111/mmi.12926;
RA Macheleidt J., Scherlach K., Neuwirth T., Schmidt-Heck W., Strassburger M.,
RA Spraker J., Baccile J.A., Schroeder F.C., Keller N.P., Hertweck C.,
RA Heinekamp T., Brakhage A.A.;
RT "Transcriptome analysis of cyclic AMP-dependent protein kinase A-regulated
RT genes reveals the production of the novel natural compound fumipyrrole by
RT Aspergillus fumigatus.";
RL Mol. Microbiol. 96:148-162(2015).
RN [3]
RP FUNCTION.
RX PubMed=27065235; DOI=10.1038/nchembio.2061;
RA Baccile J.A., Spraker J.E., Le H.H., Brandenburger E., Gomez C., Bok J.W.,
RA Macheleidt J., Brakhage A.A., Hoffmeister D., Keller N.P., Schroeder F.C.;
RT "Plant-like biosynthesis of isoquinoline alkaloids in Aspergillus
RT fumigatus.";
RL Nat. Chem. Biol. 12:419-424(2016).
RN [4]
RP FUNCTION.
RX PubMed=30194285; DOI=10.1074/jbc.ra118.004227;
RA Lahham M., Pavkov-Keller T., Fuchs M., Niederhauser J., Chalhoub G.,
RA Daniel B., Kroutil W., Gruber K., Macheroux P.;
RT "Oxidative cyclization of N-methyl-dopa by a fungal flavoenzyme of the
RT amine oxidase family.";
RL J. Biol. Chem. 293:17021-17032(2018).
CC -!- FUNCTION: ATP-grasp enzyme; part of the gene cluster that mediates the
CC biosynthesis of the isoquinoline alkaloids fumisoquin A, fumisoquin B
CC and fumisoquin C; as well as small amounts of fumipyrrole as a shunt
CC metabolite (PubMed:25582336, PubMed:27065235). The products of the
CC cluster lead to a brown coloration and are important for growth and
CC conidiation (PubMed:25582336). The nonribosomal peptide synthetase-like
CC protein fsqF, which lacks a canonical condensation domain, is required
CC for addition of a serine-derived dehydroalanine moiety to activated
CC tyrosine but is not essential for the subsequent steps leading to
CC isoquinoline formation (PubMed:27065235). A different enzyme, most
CC likely the ATP-grasp enzyme fsqD, is responsible for activation of
CC tyrosine (Probable). Three additional enzymes encoded by the fsq
CC cluster, the N-methyltransferase fsqC, the phenol 2-monooxygenase fsqG
CC and the FAD-dependent oxidase fsqB, catalyze the formation of the
CC isoquinoline ring system in the fumisoquins (PubMed:27065235,
CC PubMed:30194285). FsqB converts the fspF thiolation domain-bound
CC (2S,4S,5S)-2-amino-6-(3,4-dihydroxyphenyl)-4-hydroxy-5-
CC (methylamino)hexanoyl into isoquinoline (PubMed:27065235,
CC PubMed:30194285). The cyclization most likely proceeds via a two-step
CC mechanism, beginning with FAD-dependent oxidation of the methyl group
CC to an iminium species followed by electrophilic attack on the
CC deprotonated phenol (Probable). {ECO:0000269|PubMed:25582336,
CC ECO:0000269|PubMed:27065235, ECO:0000269|PubMed:30194285,
CC ECO:0000305|PubMed:27065235}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409};
CC Note=Binds 2 magnesium or manganese ions per subunit.
CC {ECO:0000255|PROSITE-ProRule:PRU00409};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:25582336}.
CC -!- INDUCTION: Expression is positively regulated by the fumisoquins
CC biosynthesis specific transcription factor fsqA (PubMed:25582336).
CC {ECO:0000269|PubMed:25582336, ECO:0000269|PubMed:27065235}.
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DR EMBL; AAHF01000012; EAL85693.1; -; Genomic_DNA.
DR RefSeq; XP_747731.1; XM_742638.1.
DR AlphaFoldDB; Q4WD45; -.
DR SMR; Q4WD45; -.
DR STRING; 746128.CADAFUBP00009217; -.
DR EnsemblFungi; EAL85693; EAL85693; AFUA_6G03460.
DR GeneID; 3505178; -.
DR KEGG; afm:AFUA_6G03460; -.
DR eggNOG; ENOG502QT0U; Eukaryota.
DR HOGENOM; CLU_017280_0_0_1; -.
DR InParanoid; Q4WD45; -.
DR OMA; WREAFIP; -.
DR OrthoDB; 671829at2759; -.
DR Proteomes; UP000002530; Chromosome 6.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR Gene3D; 3.30.1490.20; -; 1.
DR InterPro; IPR011761; ATP-grasp.
DR InterPro; IPR013815; ATP_grasp_subdomain_1.
DR InterPro; IPR041472; BL00235/CARNS1_N.
DR Pfam; PF18130; ATPgrasp_N; 1.
DR PROSITE; PS50975; ATP_GRASP; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Ligase; Magnesium; Manganese; Metal-binding;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..574
FT /note="ATP-grasp enzyme fsqD"
FT /id="PRO_0000438871"
FT DOMAIN 234..462
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 263..318
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 394
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 394
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 431
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 431
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 431
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 431
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 433
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 433
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
SQ SEQUENCE 574 AA; 63462 MW; 903420CF792DA76C CRC64;
MLRASASGAK CAVKLIVPLH RGFIVRSDII PLRLRDSEYV ESAVSFAEPL QTYSGKKVAI
SSRSDLTTYF AAAAAGLILR QGSTHASDAG SQALFQMVES DLANRLSFPW IQPGTPRRRT
LALVDANSSH PQDGLGFYRA ARELGINVVV LENAGHWLED PAQAHWREAF IPTRLTNPPE
EDVGDHILAS LRAYGKPVDG IVTFADSFWY YIARIAHEIG VETAPPDSMR IATNKFLTSK
YVGHDAYLAS NVDEALRIAK EVALPYPLIV KPCDGWSSEG VSRVESPDAF PAAVKSIDTS
RHGTEFVMEP YCDGPEVDVN LVLLDGEVLF AEICDDLPKS ADVNGLTVGS LTNFHELYSV
YPSALPSKEL ELLIHSFVDT LLRLGIRNGV MHLEGRVQNS SMEYREQNRM MHLQPRAPQA
TRPEPSAWLI EINPRPLGMT GSHIIESTYG IDYWGLAAVL GVGDKDRARA LSQPYRDGPQ
YTCVMVFIPA DFPPSSQGIF DTDDICADLL ARRPDLAQHI SRCATLVRRG QKVAHPTTGR
HTFLAYFNVF SRAGREEALD LARQVREEVR YSFL
