Download MendeleyThe structure of dimethylallyl tryptophan synthase reveals a common architecture of aromatic prenyltransferases in fungi and bacteria
Metzger, U., Schall, C., Zocher, G., Unsoeld, I., Stec, E., Li, S.-M., Heide, L., Stehle, T.(2009) Proc Natl Acad Sci U S A 106: 14309-14314
- PubMed: 19706516
- DOI: https://doi.org/10.1073/pnas.0904897106
- Primary Citation of Related Structures:
3I4X, 3I4Z - PubMed 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).
Organizational Affiliation:
Pharmazeutisches Institut, Universit?t T¨¹bingen, 72076 T¨¹bingen, Germany.
