Proceedings of the National Academy of Sciences - PNAS, 2009-08, Vol.106 (34), p.14309-14314
2009
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Details
- Autor(en) / Beteiligte
- Titel
- structure of dimethylallyl tryptophan synthase reveals a common architecture of aromatic prenyltransferases in fungi and bacteria
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2009-08, Vol.106 (34), p.14309-14314
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2009
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- Ergot alkaloids are toxins and important pharmaceuticals that are produced biotechnologically on an industrial scale. The first committed step of ergot alkaloid biosynthesis is catalyzed by dimethylallyl tryptophan synthase (DMATS; EC 2.5.1.34). Orthologs of DMATS are found in many fungal genomes. We report here the x-ray structure of DMATS, determined at a resolution of 1.76 Å. A complex of DMATS from Aspergillus fumigatus with its aromatic substrate L-tryptophan and with an analogue of its isoprenoid substrate dimethylallyl diphosphate reveals the structural basis of this enzyme-catalyzed Friedel-Crafts reaction, which shows strict regiospecificity for position 4 of the indole nucleus of tryptophan as well as unusual independence of the presence of Mg²⁺ ions. The 3D structure of DMATS belongs to a rare β/α barrel fold, called prenyltransferase barrel, that was recently discovered in a small group of bacterial enzymes with no sequence similarity to DMATS. These bacterial enzymes catalyze the prenylation of aromatic substrates in the biosynthesis of secondary metabolites (i.e., a reaction similar to that of DMATS).
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.0904897106Titel-ID: cdi_pnas_primary_106_34_14309
- Format
- –
- Schlagworte
- Active sites, Alkalies, Alkyl and Aryl Transferases - chemistry, Alkyl and Aryl Transferases - genetics, Alkyl and Aryl Transferases - metabolism, Amino Acid Sequence, Aspergillus fumigatus, Aspergillus fumigatus - enzymology, Aspergillus fumigatus - genetics, Bacteria, Bacteria - enzymology, Biological Sciences, Biosynthesis, Biotechnology, Catalysis, Catalytic Domain, Chemical synthesis, Claviceps, Crystallography, X-Ray, Dimethylallyltranstransferase - chemistry, Dimethylallyltranstransferase - genetics, Dimethylallyltranstransferase - metabolism, Diphosphates, Enzyme substrates, Enzymes, Ergot alkaloids, Fungal Proteins - chemistry, Fungal Proteins - genetics, Fungal Proteins - metabolism, Fungi, Fungi - enzymology, Hemiterpenes - chemistry, Hemiterpenes - metabolism, Hydrogen bonds, Indoles, Magnesium - chemistry, Models, Chemical, Models, Molecular, Molecular Sequence Data, Molecular Structure, Organophosphorus Compounds - chemistry, Organophosphorus Compounds - metabolism, Protein Structure, Tertiary, Proteins, Sequence Homology, Amino Acid, Substrate Specificity, Terpenes - chemistry, Terpenes - metabolism, Tryptophan - chemistry, Tryptophan - metabolism