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Protein

Tryptophan dimethylallyltransferase

Gene

dmaW

Organism
Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100) (Aspergillus fumigatus)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Tryptophan dimethylallyltransferase; part of the gene cluster that mediates the biosynthesis of fumiclavanine C, a fungal ergot alkaloid (PubMed:15933009, PubMed:23435153, PubMed:26972831). DmaW catalyzes the first step of ergot alkaloid biosynthesis by condensing dimethylallyl diphosphate (DMAP) and tryptophan to form 4-dimethylallyl-L-tryptophan (PubMed:15870460, PubMed:23435153). The second step is catalyzed by the methyltransferase easF that methylates 4-dimethylallyl-L-tryptophan in the presence of S-adenosyl-L-methionine, resulting in the formation of 4-dimethylallyl-L-abrine (By similarity). The catalase easC and the FAD-dependent oxidoreductase easE then transform 4-dimethylallyl-L-abrine to chanoclavine-I which is further oxidized by EasD in the presence of NAD+, resulting in the formation of chanoclavine-I aldehyde (PubMed:20039019, PubMed:20526482, PubMed:21409592). EasA reduces chanoclavine-I aldehyde to dihydrochanoclavine-I aldehyde that spontaneously dehydrates to form 6,8-dimethyl-6,7-didehydroergoline (PubMed:20526482). EasG then catalyzes the reduction of 6,8-dimethyl-6,7-didehydroergoline to form festuclavine (PubMed:20526482). Hydrolysis of festuclavine by easM then leads to the formation of fumigaclavine B which is in turn acetylated by easN to fumigaclavine A (PubMed:26972831). Finally, easL catalyzes the conversion of fumigaclavine A into fumigaclavine C by attaching a dimethylallyl moiety to C-2 of the indole nucleus (PubMed:19672909).By similarity8 Publications

Catalytic activityi

Dimethylallyl diphosphate + L-tryptophan = diphosphate + 4-(3-methylbut-2-enyl)-L-tryptophan.1 Publication

Kineticsi

  1. KM=4 µM for dimethylallyl diphosphate1 Publication
  2. KM=8 µM for L-tryptophan1 Publication
  1. Vmax=0.198 µmol/min/mg enzyme1 Publication

Pathwayi: ergot alkaloid biosynthesis

This protein is involved in the pathway ergot alkaloid biosynthesis, which is part of Alkaloid biosynthesis.2 Publications
View all proteins of this organism that are known to be involved in the pathway ergot alkaloid biosynthesis and in Alkaloid biosynthesis.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei89 – 891L-tryptophan1 Publication
Binding sitei100 – 1001Substrate1 Publication
Binding sitei187 – 1871Substrate1 Publication
Binding sitei189 – 1891Substrate1 Publication
Binding sitei191 – 1911L-tryptophan1 Publication
Binding sitei244 – 2441L-tryptophan1 Publication
Binding sitei257 – 2571Substrate1 Publication
Binding sitei259 – 2591Substrate1 Publication
Binding sitei261 – 2611Substrate1 Publication
Binding sitei343 – 3431Substrate1 Publication
Binding sitei345 – 3451Substrate1 Publication
Binding sitei409 – 4091Substrate1 Publication
Binding sitei413 – 4131Substrate1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Alkaloid metabolism

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-15369.
BRENDAi2.5.1.34. 508.
SABIO-RKQ50EL0.
UniPathwayiUPA00327.

Protein family/group databases

MEROPSiM77.004.

Names & Taxonomyi

Protein namesi
Recommended name:
Tryptophan dimethylallyltransferaseCurated (EC:2.5.1.341 Publication)
Alternative name(s):
4-dimethylallyltryptophan synthase1 Publication
All-trans-hexaprenyl-diphosphate synthaseCurated
L-tryptophan dimethylallyl transferaseCurated
Short name:
DMATSCurated
Gene namesi
Name:dmaW1 Publication
Synonyms:fgaPT21 Publication
ORF Names:AFUA_2G18040
OrganismiNeosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100) (Aspergillus fumigatus)
Taxonomic identifieri330879 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaPezizomycotinaEurotiomycetesEurotiomycetidaeEurotialesAspergillaceaeAspergillus
Proteomesi
  • UP000002530 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiFungiDB:Afu2g18040.

Pathology & Biotechi

Biotechnological usei

Ergot alkaloids are known for their toxic effects on humans who consume contaminated grains or livestock that graze on grasses harboring ergot alkaloid-producing fungi (PubMed:19523108). Due to their strong affinity for monoamine neurotransmitter receptors they may also have clinical uses such as treatment of migraines, Parkinson's disease and cerebrovascular insufficiency (PubMed:19523108).1 Publication

Disruption phenotypei

Impairs the production of ergot alkaloids including festuclavine, fumigaclavine A, fumigaclavine B and fumigaclavine C (PubMed:15933009).1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi89 – 891E → A: Abolishes tryptophan dimethylallyltransferase activity. 1 Publication
Mutagenesisi100 – 1001R → D or Q: Nearly abolishes tryptophan dimethylallyltransferase activity. 1 Publication
Mutagenesisi174 – 1741K → E: Nearly abolishess tryptophan dimethylallyltransferase activity. 1 Publication
Mutagenesisi174 – 1741K → Q: Impairs tryptophan dimethylallyltransferase activity. 1 Publication
Mutagenesisi187 – 1871K → E: Nearly abolishes tryptophan dimethylallyltransferase activity. 1 Publication
Mutagenesisi259 – 2591K → E: Nearly abolishes tryptophan dimethylallyltransferase activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 459459Tryptophan dimethylallyltransferasePRO_0000228687Add
BLAST

Expressioni

Inductioni

The expression of the ergot alkaloid synthesis cluster which leads to the synthesis of fumigaclavines is positively regulated by the brlA and stuA transcritpion factors (PubMed:19028996).1 Publication

Interactioni

Subunit structurei

Homodimer.2 Publications

Structurei

Secondary structure

1
459
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi6 – 83Combined sources
Helixi10 – 189Combined sources
Helixi24 – 4320Combined sources
Helixi48 – 6114Combined sources
Helixi63 – 653Combined sources
Beta strandi72 – 743Combined sources
Beta strandi87 – 937Combined sources
Turni94 – 974Combined sources
Beta strandi98 – 1036Combined sources
Helixi122 – 1298Combined sources
Helixi130 – 1323Combined sources
Helixi139 – 14810Combined sources
Helixi152 – 1609Combined sources
Helixi162 – 1643Combined sources
Turni165 – 1673Combined sources
Beta strandi173 – 1808Combined sources
Beta strandi183 – 1908Combined sources
Helixi193 – 1997Combined sources
Helixi203 – 21715Combined sources
Helixi219 – 2213Combined sources
Helixi222 – 23413Combined sources
Beta strandi240 – 25112Combined sources
Turni253 – 2553Combined sources
Beta strandi258 – 2647Combined sources
Beta strandi266 – 2683Combined sources
Helixi269 – 2768Combined sources
Turni277 – 2815Combined sources
Helixi285 – 30117Combined sources
Beta strandi327 – 3337Combined sources
Beta strandi341 – 3466Combined sources
Helixi353 – 36614Combined sources
Helixi370 – 38314Combined sources
Helixi389 – 3913Combined sources
Beta strandi394 – 40411Combined sources
Beta strandi407 – 4148Combined sources
Helixi420 – 4245Combined sources
Helixi448 – 4503Combined sources
Beta strandi451 – 4544Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3I4XX-ray2.10A/B1-459[»]
3I4ZX-ray1.76A/B1-459[»]
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ50EL0.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni80 – 812L-tryptophan binding1 Publication

Sequence similaritiesi

Phylogenomic databases

HOGENOMiHOG000200278.
InParanoidiQ50EL0.
KOiK14130.
OrthoDBiEOG7HTHSG.

Family and domain databases

InterProiIPR017795. Aromatic_prenylTrfase_DMATS.
IPR012148. Trp_dimethylallyltransferase.
IPR017796. Trp_dimethylallylTrfase_sub.
[Graphical view]
PfamiPF11991. Trp_DMAT. 1 hit.
[Graphical view]
PIRSFiPIRSF000509. Trp_DMAT. 1 hit.
TIGRFAMsiTIGR03429. arom_pren_DMATS. 1 hit.
TIGR03430. trp_dimet_allyl. 1 hit.

Sequencei

Sequence statusi: Complete.

Q50EL0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKAANASSAE AYRVLSRAFR FDNEDQKLWW HSTAPMFAKM LETANYTTPC
60 70 80 90 100
QYQYLITYKE CVIPSLGCYP TNSAPRWLSI LTRYGTPFEL SLNCSNSIVR
110 120 130 140 150
YTFEPINQHT GTDKDPFNTH AIWESLQHLL PLEKSIDLEW FRHFKHDLTL
160 170 180 190 200
NSEESAFLAH NDRLVGGTIR TQNKLALDLK DGRFALKTYI YPALKAVVTG
210 220 230 240 250
KTIHELVFGS VRRLAVREPR ILPPLNMLEE YIRSRGSKST ASPRLVSCDL
260 270 280 290 300
TSPAKSRIKI YLLEQMVSLE AMEDLWTLGG RRRDASTLEG LSLVRELWDL
310 320 330 340 350
IQLSPGLKSY PAPYLPLGVI PDERLPLMAN FTLHQNDPVP EPQVYFTTFG
360 370 380 390 400
MNDMAVADAL TTFFERRGWS EMARTYETTL KSYYPHADHD KLNYLHAYIS
410 420 430 440 450
FSYRDRTPYL SVYLQSFETG DWAVANLSES KVKCQDAACQ PTSLPPDLSK

TGVYYSGLH
Length:459
Mass (Da):52,463
Last modified:March 21, 2006 - v2
Checksum:iED7AAB193E9A46C8
GO

Sequence cautioni

The sequence EAL94103.2 differs from that shown. Reason: Erroneous gene model prediction. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti443 – 4431S → A in strain: B5233 / ATCC 13073.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY775787 mRNA. Translation: AAX08549.1.
AAHF01000001 Genomic DNA. Translation: EAL94103.2. Sequence problems.
RefSeqiXP_756141.2. XM_751048.2.

Genome annotation databases

GeneIDi3512716.
KEGGiafm:AFUA_2G18040.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY775787 mRNA. Translation: AAX08549.1.
AAHF01000001 Genomic DNA. Translation: EAL94103.2. Sequence problems.
RefSeqiXP_756141.2. XM_751048.2.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3I4XX-ray2.10A/B1-459[»]
3I4ZX-ray1.76A/B1-459[»]
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiM77.004.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi3512716.
KEGGiafm:AFUA_2G18040.

Organism-specific databases

EuPathDBiFungiDB:Afu2g18040.

Phylogenomic databases

HOGENOMiHOG000200278.
InParanoidiQ50EL0.
KOiK14130.
OrthoDBiEOG7HTHSG.

Enzyme and pathway databases

UniPathwayiUPA00327.
BioCyciMetaCyc:MONOMER-15369.
BRENDAi2.5.1.34. 508.
SABIO-RKQ50EL0.

Miscellaneous databases

EvolutionaryTraceiQ50EL0.

Family and domain databases

InterProiIPR017795. Aromatic_prenylTrfase_DMATS.
IPR012148. Trp_dimethylallyltransferase.
IPR017796. Trp_dimethylallylTrfase_sub.
[Graphical view]
PfamiPF11991. Trp_DMAT. 1 hit.
[Graphical view]
PIRSFiPIRSF000509. Trp_DMAT. 1 hit.
TIGRFAMsiTIGR03429. arom_pren_DMATS. 1 hit.
TIGR03430. trp_dimet_allyl. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Overproduction, purification and characterization of FgaPT2, a dimethylallyltryptophan synthase from Aspergillus fumigatus."
    Unsoeld I.A., Li S.-M.
    Microbiology 151:1499-1505(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PATHWAY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, CATALYTIC ACTIVITY.
    Strain: B5233 / ATCC 13073.
  2. "Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus."
    Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J., Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P., Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.
    , Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N., Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K., Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E., Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H., Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A., Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L., Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D., O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L., Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U., Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M., Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C., Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F., Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R., Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N., Barrell B.G., Denning D.W.
    Nature 438:1151-1156(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100.
  3. "An ergot alkaloid biosynthesis gene and clustered hypothetical genes from Aspergillus fumigatus."
    Coyle C.M., Panaccione D.G.
    Appl. Environ. Microbiol. 71:3112-3118(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION, FUNCTION, DISRUPTION PHENOTYPE.
  4. "Two lysine residues are responsible for the enzymatic activities of indole prenyltransferases from fungi."
    Stec E., Steffan N., Kremer A., Zou H., Zheng X., Li S.M.
    ChemBioChem 9:2055-2058(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF LYS-187 AND LYS-259.
  5. "Ergot alkaloid biosynthesis in Aspergillus fumigatus: FgaAT catalyses the acetylation of fumigaclavine B."
    Liu X., Wang L., Steffan N., Yin W.B., Li S.M.
    ChemBioChem 10:2325-2328(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Transcriptional profiling identifies a role for BrlA in the response to nitrogen depletion and for StuA in the regulation of secondary metabolite clusters in Aspergillus fumigatus."
    Twumasi-Boateng K., Yu Y., Chen D., Gravelat F.N., Nierman W.C., Sheppard D.C.
    Eukaryot. Cell 8:104-115(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  7. Cited for: BIOTECHNOLOGY.
  8. "Ergot alkaloid biosynthesis in Aspergillus fumigatus: conversion of chanoclavine-I to chanoclavine-I aldehyde catalyzed by a short-chain alcohol dehydrogenase FgaDH."
    Wallwey C., Matuschek M., Li S.M.
    Arch. Microbiol. 192:127-134(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Ergot alkaloid biosynthesis in Aspergillus fumigatus: Conversion of chanoclavine-I aldehyde to festuclavine by the festuclavine synthase FgaFS in the presence of the old yellow enzyme FgaOx3."
    Wallwey C., Matuschek M., Xie X.L., Li S.M.
    Org. Biomol. Chem. 8:3500-3508(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, NOMENCLATURE.
  10. "Ergot cluster-encoded catalase is required for synthesis of chanoclavine-I in Aspergillus fumigatus."
    Goetz K.E., Coyle C.M., Cheng J.Z., O'Connor S.E., Panaccione D.G.
    Curr. Genet. 57:201-211(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. "Chemotypic and genotypic diversity in the ergot alkaloid pathway of Aspergillus fumigatus."
    Robinson S.L., Panaccione D.G.
    Mycologia 104:804-812(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION, NOMENCLATURE.
  12. "Partial reconstruction of the ergot alkaloid pathway by heterologous gene expression in Aspergillus nidulans."
    Ryan K.L., Moore C.T., Panaccione D.G.
    Toxins 5:445-455(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PATHWAY.
  13. "Functional analysis of the gene controlling hydroxylation of festuclavine in the ergot alkaloid pathway of Neosartorya fumigata."
    Bilovol Y., Panaccione D.G.
    Curr. Genet. 0:0-0(2016) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  14. "The structure of dimethylallyl tryptophan synthase reveals a common architecture of aromatic prenyltransferases in fungi and bacteria."
    Metzger U., Schall C., Zocher G., Unsold I., Stec E., Li S.M., Heide L., Stehle T.
    Proc. Natl. Acad. Sci. U.S.A. 106:14309-14314(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH TRYPTOPHAN AND DIMETHYLALLYL S-THIOLODIPHOSPHATE, SUBUNIT, MUTAGENESIS OF GLU-89; ARG-100 AND LYS-174.

Entry informationi

Entry nameiDMAW_ASPFU
AccessioniPrimary (citable) accession number: Q50EL0
Secondary accession number(s): Q4WZ62
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: March 21, 2006
Last modified: June 8, 2016
This is version 67 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.