title: The structure of dimethylallyl tryptophan synthase reveals a common architecture of aromatic prenyltransferases in fungi and bacteria.
abstract: 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 A. 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 Mg(2+) ions. The 3D structure of DMATS belongs to a rare beta/alpha 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).
authors.affiliation: Pharmazeutisches Institut, Universität Tübingen, 72076 Tübingen, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Metzger
authors.forename: Christoph
authors.initials: C
authors.lastname: Schall
authors.forename: Georg
authors.initials: G
authors.lastname: Zocher
authors.forename: Inge
authors.initials: I
authors.lastname: Unsöld
authors.forename: Edyta
authors.initials: E
authors.lastname: Stec
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: Li
authors.forename: Lutz
authors.initials: L
authors.lastname: Heide
authors.forename: Thilo
authors.initials: T
authors.lastname: Stehle
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001232:Aspergillus fumigatus / Q000201:enzymology* / Q000235:genetics; D001419:Bacteria / Q000201:enzymology; D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004122:Dimethylallyltranstransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005658:Fungi / Q000201:enzymology; D045782:Hemiterpenes / Q000737:chemistry / Q000378:metabolism; D008274:Magnesium / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D013729:Terpenes / Q000737:chemistry / Q000378:metabolism; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D045782:Hemiterpenes; D009943:Organophosphorus Compounds; D013729:Terpenes; C043060:3,3-dimethylallyl pyrophosphate; D014364:Tryptophan; D019883:Alkyl and Aryl Transferases; D004122:Dimethylallyltranstransferase; C032409:tryptophan dimethylallyltransferase; D008274:Magnesium
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