The structure of dimethylallyl tryptophan synthase reveals a common architecture of aromatic prenyltransferases in fungi and bacteria
The structure of dimethylallyl tryptophan synthase reveals a common architecture of aromatic prenyltransferases in fungi and bacteria
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DOI：
10.1073/pnas.0904897106
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发表时间：
2009-08-25
影响因子：
11.1
通讯作者：
Stehle, Thilo
中科院分区：
文献类型：
--
作者：
Metzger, Ute;Schall, Christoph;Stehle, Thilo
麦角生物碱是毒素和重要的药物，是在工业规模上通过生物技术生产的。麦角生物碱合成的第一步是由二甲基烯丙基色氨酸合成酶（DMATS; EC 2.5.1.34）催化。在许多真菌基因组中发现了DMATS的同源物。我们在这里报告了DMATS的x射线结构，以1.76埃的分辨率确定。烟曲霉DMATS与其芳香底物l-色氨酸和类似物异戊二烯类底物二磷酸二甲基丙烯的配合物揭示了这种酶催化的Friedel-Crafts反应的结构基础，该反应对色氨酸吲哚核的4位具有严格的区域特异性，并且对Mg2+离子的存在具有不同寻常的独立性。DMATS的三维结构属于一种罕见的β / α桶状折叠，称为prenyltransferase barrel，这是最近在一小群与DMATS没有序列相似性的细菌酶中发现的。这些细菌酶在次生代谢产物的生物合成中催化芳香底物的戊烯酰化（即类似于DMATS的反应）。
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 angstrom. 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 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).