DMAW_ASPFU
ID DMAW_ASPFU Reviewed; 459 AA.
AC Q50EL0; Q4WZ62;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Tryptophan dimethylallyltransferase {ECO:0000305};
DE EC=2.5.1.34 {ECO:0000269|PubMed:15870460};
DE AltName: Full=4-dimethylallyltryptophan synthase {ECO:0000303|PubMed:15870460};
DE AltName: Full=All-trans-hexaprenyl-diphosphate synthase {ECO:0000305};
DE AltName: Full=L-tryptophan dimethylallyl transferase {ECO:0000305};
DE Short=DMATS {ECO:0000305};
GN Name=dmaW {ECO:0000303|PubMed:22453123};
GN Synonyms=fgaPT2 {ECO:0000303|PubMed:20526482}; ORFNames=AFUA_2G18040;
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 [MRNA], FUNCTION, PATHWAY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, AND CATALYTIC ACTIVITY.
RC STRAIN=B5233 / ATCC 13073;
RX PubMed=15870460; DOI=10.1099/mic.0.27759-0;
RA Unsoeld I.A., Li S.-M.;
RT "Overproduction, purification and characterization of FgaPT2, a
RT dimethylallyltryptophan synthase from Aspergillus fumigatus.";
RL Microbiology 151:1499-1505(2005).
RN [2]
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 [3]
RP IDENTIFICATION, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15933009; DOI=10.1128/aem.71.6.3112-3118.2005;
RA Coyle C.M., Panaccione D.G.;
RT "An ergot alkaloid biosynthesis gene and clustered hypothetical genes from
RT Aspergillus fumigatus.";
RL Appl. Environ. Microbiol. 71:3112-3118(2005).
RN [4]
RP MUTAGENESIS OF LYS-187 AND LYS-259.
RX PubMed=18677738; DOI=10.1002/cbic.200800237;
RA Stec E., Steffan N., Kremer A., Zou H., Zheng X., Li S.M.;
RT "Two lysine residues are responsible for the enzymatic activities of indole
RT prenyltransferases from fungi.";
RL ChemBioChem 9:2055-2058(2008).
RN [5]
RP FUNCTION.
RX PubMed=19672909; DOI=10.1002/cbic.200900395;
RA Liu X., Wang L., Steffan N., Yin W.B., Li S.M.;
RT "Ergot alkaloid biosynthesis in Aspergillus fumigatus: FgaAT catalyses the
RT acetylation of fumigaclavine B.";
RL ChemBioChem 10:2325-2328(2009).
RN [6]
RP INDUCTION.
RX PubMed=19028996; DOI=10.1128/ec.00265-08;
RA Twumasi-Boateng K., Yu Y., Chen D., Gravelat F.N., Nierman W.C.,
RA Sheppard D.C.;
RT "Transcriptional profiling identifies a role for BrlA in the response to
RT nitrogen depletion and for StuA in the regulation of secondary metabolite
RT clusters in Aspergillus fumigatus.";
RL Eukaryot. Cell 8:104-115(2009).
RN [7]
RP BIOTECHNOLOGY.
RX PubMed=19523108; DOI=10.1111/j.1364-3703.2009.00548.x;
RA Haarmann T., Rolke Y., Giesbert S., Tudzynski P.;
RT "Ergot: from witchcraft to biotechnology.";
RL Mol. Plant Pathol. 10:563-577(2009).
RN [8]
RP FUNCTION.
RX PubMed=20039019; DOI=10.1007/s00203-009-0536-1;
RA Wallwey C., Matuschek M., Li S.M.;
RT "Ergot alkaloid biosynthesis in Aspergillus fumigatus: conversion of
RT chanoclavine-I to chanoclavine-I aldehyde catalyzed by a short-chain
RT alcohol dehydrogenase FgaDH.";
RL Arch. Microbiol. 192:127-134(2010).
RN [9]
RP FUNCTION, AND NOMENCLATURE.
RX PubMed=20526482; DOI=10.1039/c003823g;
RA Wallwey C., Matuschek M., Xie X.L., Li S.M.;
RT "Ergot alkaloid biosynthesis in Aspergillus fumigatus: Conversion of
RT chanoclavine-I aldehyde to festuclavine by the festuclavine synthase FgaFS
RT in the presence of the old yellow enzyme FgaOx3.";
RL Org. Biomol. Chem. 8:3500-3508(2010).
RN [10]
RP FUNCTION.
RX PubMed=21409592; DOI=10.1007/s00294-011-0336-4;
RA Goetz K.E., Coyle C.M., Cheng J.Z., O'Connor S.E., Panaccione D.G.;
RT "Ergot cluster-encoded catalase is required for synthesis of chanoclavine-I
RT in Aspergillus fumigatus.";
RL Curr. Genet. 57:201-211(2011).
RN [11]
RP IDENTIFICATION, AND NOMENCLATURE.
RX PubMed=22453123; DOI=10.3852/11-310;
RA Robinson S.L., Panaccione D.G.;
RT "Chemotypic and genotypic diversity in the ergot alkaloid pathway of
RT Aspergillus fumigatus.";
RL Mycologia 104:804-812(2012).
RN [12]
RP FUNCTION, AND PATHWAY.
RX PubMed=23435153; DOI=10.3390/toxins5020445;
RA Ryan K.L., Moore C.T., Panaccione D.G.;
RT "Partial reconstruction of the ergot alkaloid pathway by heterologous gene
RT expression in Aspergillus nidulans.";
RL Toxins 5:445-455(2013).
RN [13]
RP FUNCTION.
RX PubMed=26972831; DOI=10.1007/s00294-016-0591-5;
RA Bilovol Y., Panaccione D.G.;
RT "Functional analysis of the gene controlling hydroxylation of festuclavine
RT in the ergot alkaloid pathway of Neosartorya fumigata.";
RL Curr. Genet. 62:853-860(2016).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH TRYPTOPHAN AND
RP DIMETHYLALLYL S-THIOLODIPHOSPHATE, SUBUNIT, AND MUTAGENESIS OF GLU-89;
RP ARG-100 AND LYS-174.
RX PubMed=19706516; DOI=10.1073/pnas.0904897106;
RA Metzger U., Schall C., Zocher G., Unsold I., Stec E., Li S.M., Heide L.,
RA Stehle T.;
RT "The structure of dimethylallyl tryptophan synthase reveals a common
RT architecture of aromatic prenyltransferases in fungi and bacteria.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:14309-14314(2009).
CC -!- FUNCTION: Tryptophan dimethylallyltransferase; part of the gene cluster
CC that mediates the biosynthesis of fumiclavanine C, a fungal ergot
CC alkaloid (PubMed:15933009, PubMed:23435153, PubMed:26972831). DmaW
CC catalyzes the first step of ergot alkaloid biosynthesis by condensing
CC dimethylallyl diphosphate (DMAP) and tryptophan to form 4-
CC dimethylallyl-L-tryptophan (PubMed:15870460, PubMed:23435153). The
CC second step is catalyzed by the methyltransferase easF that methylates
CC 4-dimethylallyl-L-tryptophan in the presence of S-adenosyl-L-
CC methionine, resulting in the formation of 4-dimethylallyl-L-abrine (By
CC similarity). The catalase easC and the FAD-dependent oxidoreductase
CC easE then transform 4-dimethylallyl-L-abrine to chanoclavine-I which is
CC further oxidized by EasD in the presence of NAD(+), resulting in the
CC formation of chanoclavine-I aldehyde (PubMed:20039019, PubMed:20526482,
CC PubMed:21409592). EasA reduces chanoclavine-I aldehyde to
CC dihydrochanoclavine-I aldehyde that spontaneously dehydrates to form
CC 6,8-dimethyl-6,7-didehydroergoline (PubMed:20526482). EasG then
CC catalyzes the reduction of 6,8-dimethyl-6,7-didehydroergoline to form
CC festuclavine (PubMed:20526482). Hydrolysis of festuclavine by easM then
CC leads to the formation of fumigaclavine B which is in turn acetylated
CC by easN to fumigaclavine A (PubMed:26972831). Finally, easL catalyzes
CC the conversion of fumigaclavine A into fumigaclavine C by attaching a
CC dimethylallyl moiety to C-2 of the indole nucleus (PubMed:19672909).
CC {ECO:0000250|UniProtKB:B6D5I7, ECO:0000269|PubMed:15870460,
CC ECO:0000269|PubMed:15933009, ECO:0000269|PubMed:19672909,
CC ECO:0000269|PubMed:20039019, ECO:0000269|PubMed:20526482,
CC ECO:0000269|PubMed:21409592, ECO:0000269|PubMed:23435153,
CC ECO:0000269|PubMed:26972831}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dimethylallyl diphosphate + L-tryptophan = 4-(3-methylbut-2-
CC enyl)-L-tryptophan + diphosphate; Xref=Rhea:RHEA:14173,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57623, ChEBI:CHEBI:57912,
CC ChEBI:CHEBI:58209; EC=2.5.1.34;
CC Evidence={ECO:0000269|PubMed:15870460};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4 uM for dimethylallyl diphosphate {ECO:0000269|PubMed:15870460};
CC KM=8 uM for L-tryptophan {ECO:0000269|PubMed:15870460};
CC Vmax=0.198 umol/min/mg enzyme {ECO:0000269|PubMed:15870460};
CC -!- PATHWAY: Alkaloid biosynthesis; ergot alkaloid biosynthesis.
CC {ECO:0000269|PubMed:15870460, ECO:0000269|PubMed:23435153}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15870460,
CC ECO:0000269|PubMed:19706516}.
CC -!- INDUCTION: The expression of the ergot alkaloid synthesis cluster which
CC leads to the synthesis of fumigaclavines is positively regulated by the
CC brlA and stuA transcription factors (PubMed:19028996).
CC {ECO:0000269|PubMed:19028996}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of ergot alkaloids
CC including festuclavine, fumigaclavine A, fumigaclavine B and
CC fumigaclavine C (PubMed:15933009). {ECO:0000269|PubMed:15933009}.
CC -!- BIOTECHNOLOGY: Ergot alkaloids are known for their toxic effects on
CC humans who consume contaminated grains or livestock that graze on
CC grasses harboring ergot alkaloid-producing fungi (PubMed:19523108). Due
CC to their strong affinity for monoamine neurotransmitter receptors they
CC may also have clinical uses such as treatment of migraines, Parkinson's
CC disease and cerebrovascular insufficiency (PubMed:19523108).
CC {ECO:0000305|PubMed:19523108}.
CC -!- SIMILARITY: Belongs to the tryptophan dimethylallyltransferase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAL94103.2; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AY775787; AAX08549.1; -; mRNA.
DR EMBL; AAHF01000001; EAL94103.2; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_756141.2; XM_751048.2.
DR PDB; 3I4X; X-ray; 2.10 A; A/B=1-459.
DR PDB; 3I4Z; X-ray; 1.76 A; A/B=1-459.
DR PDBsum; 3I4X; -.
DR PDBsum; 3I4Z; -.
DR AlphaFoldDB; Q50EL0; -.
DR SMR; Q50EL0; -.
DR STRING; 746128.CADAFUBP00003306; -.
DR ChEMBL; CHEMBL4523316; -.
DR PRIDE; Q50EL0; -.
DR GeneID; 3512716; -.
DR KEGG; afm:AFUA_2G18040; -.
DR eggNOG; ENOG502S2XP; Eukaryota.
DR HOGENOM; CLU_037431_0_0_1; -.
DR InParanoid; Q50EL0; -.
DR OrthoDB; 1531660at2759; -.
DR BioCyc; MetaCyc:MON-15369; -.
DR BRENDA; 2.5.1.34; 508.
DR SABIO-RK; Q50EL0; -.
DR UniPathway; UPA00327; -.
DR EvolutionaryTrace; Q50EL0; -.
DR Proteomes; UP000002530; Chromosome 2.
DR GO; GO:0004659; F:prenyltransferase activity; IEA:UniProt.
DR GO; GO:0050364; F:tryptophan dimethylallyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:1900809; P:fumigaclavine C biosynthetic process; IDA:GO_Central.
DR CDD; cd13929; PT-DMATS_CymD; 1.
DR InterPro; IPR033964; Aro_prenylTrfase.
DR InterPro; IPR017795; Aro_prenylTrfase_DMATS.
DR InterPro; IPR012148; DMATS-type_fun.
DR InterPro; IPR017796; Trp_dimethylallylTrfase.
DR PANTHER; PTHR40627; PTHR40627; 1.
DR Pfam; PF11991; Trp_DMAT; 1.
DR PIRSF; PIRSF000509; Trp_DMAT; 1.
DR SFLD; SFLDS00036; Aromatic_Prenyltransferase; 1.
DR TIGRFAMs; TIGR03429; arom_pren_DMATS; 1.
DR TIGRFAMs; TIGR03430; trp_dimet_allyl; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alkaloid metabolism; Reference proteome; Transferase.
FT CHAIN 1..459
FT /note="Tryptophan dimethylallyltransferase"
FT /id="PRO_0000228687"
FT BINDING 80..81
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000269|PubMed:19706516"
FT BINDING 89
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000269|PubMed:19706516"
FT BINDING 100
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19706516"
FT BINDING 187
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19706516"
FT BINDING 189
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19706516"
FT BINDING 191
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000269|PubMed:19706516"
FT BINDING 244
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000269|PubMed:19706516"
FT BINDING 257
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19706516"
FT BINDING 259
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19706516"
FT BINDING 261
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19706516"
FT BINDING 343
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19706516"
FT BINDING 345
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19706516"
FT BINDING 409
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19706516"
FT BINDING 413
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19706516"
FT VARIANT 443
FT /note="S -> A (in strain: B5233 / ATCC 13073)"
FT MUTAGEN 89
FT /note="E->A: Abolishes tryptophan dimethylallyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:19706516"
FT MUTAGEN 100
FT /note="R->D,Q: Nearly abolishes tryptophan
FT dimethylallyltransferase activity."
FT /evidence="ECO:0000269|PubMed:19706516"
FT MUTAGEN 174
FT /note="K->E: Nearly abolishess tryptophan
FT dimethylallyltransferase activity."
FT /evidence="ECO:0000269|PubMed:19706516"
FT MUTAGEN 174
FT /note="K->Q: Impairs tryptophan dimethylallyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:19706516"
FT MUTAGEN 187
FT /note="K->E: Nearly abolishes tryptophan
FT dimethylallyltransferase activity."
FT /evidence="ECO:0000269|PubMed:18677738"
FT MUTAGEN 259
FT /note="K->E: Nearly abolishes tryptophan
FT dimethylallyltransferase activity."
FT /evidence="ECO:0000269|PubMed:18677738"
FT HELIX 6..8
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 10..18
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 24..43
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 48..61
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:3I4Z"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:3I4Z"
FT STRAND 87..93
FT /evidence="ECO:0007829|PDB:3I4Z"
FT TURN 94..97
FT /evidence="ECO:0007829|PDB:3I4Z"
FT STRAND 98..103
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 122..129
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 130..132
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 139..148
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 152..160
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:3I4Z"
FT TURN 165..167
FT /evidence="ECO:0007829|PDB:3I4Z"
FT STRAND 173..180
FT /evidence="ECO:0007829|PDB:3I4Z"
FT STRAND 183..190
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 193..199
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 203..217
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 219..221
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 222..234
FT /evidence="ECO:0007829|PDB:3I4Z"
FT STRAND 240..251
FT /evidence="ECO:0007829|PDB:3I4Z"
FT TURN 253..255
FT /evidence="ECO:0007829|PDB:3I4Z"
FT STRAND 258..264
FT /evidence="ECO:0007829|PDB:3I4Z"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 269..276
FT /evidence="ECO:0007829|PDB:3I4Z"
FT TURN 277..281
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 285..301
FT /evidence="ECO:0007829|PDB:3I4Z"
FT STRAND 327..333
FT /evidence="ECO:0007829|PDB:3I4Z"
FT STRAND 341..346
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 353..366
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 370..383
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 389..391
FT /evidence="ECO:0007829|PDB:3I4Z"
FT STRAND 394..404
FT /evidence="ECO:0007829|PDB:3I4Z"
FT STRAND 407..414
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 420..424
FT /evidence="ECO:0007829|PDB:3I4Z"
FT HELIX 448..450
FT /evidence="ECO:0007829|PDB:3I4Z"
FT STRAND 451..454
FT /evidence="ECO:0007829|PDB:3I4Z"
SQ SEQUENCE 459 AA; 52463 MW; ED7AAB193E9A46C8 CRC64;
MKAANASSAE AYRVLSRAFR FDNEDQKLWW HSTAPMFAKM LETANYTTPC QYQYLITYKE
CVIPSLGCYP TNSAPRWLSI LTRYGTPFEL SLNCSNSIVR YTFEPINQHT GTDKDPFNTH
AIWESLQHLL PLEKSIDLEW FRHFKHDLTL NSEESAFLAH NDRLVGGTIR TQNKLALDLK
DGRFALKTYI YPALKAVVTG KTIHELVFGS VRRLAVREPR ILPPLNMLEE YIRSRGSKST
ASPRLVSCDL TSPAKSRIKI YLLEQMVSLE AMEDLWTLGG RRRDASTLEG LSLVRELWDL
IQLSPGLKSY PAPYLPLGVI PDERLPLMAN FTLHQNDPVP EPQVYFTTFG MNDMAVADAL
TTFFERRGWS EMARTYETTL KSYYPHADHD KLNYLHAYIS FSYRDRTPYL SVYLQSFETG
DWAVANLSES KVKCQDAACQ PTSLPPDLSK TGVYYSGLH
