Lundqvist T, Rice J, Hodge C N, Basarab G S, Pierce J, Lindqvist Y
Department of Molecular Biology, Swedish University of Agricultural Sciences Uppsala Biomedical Center.
Structure. 1994 Oct 15;2(10):937-44. doi: 10.1016/s0969-2126(94)00095-6.
Rice blast is caused by the pathogenic fungus,-Magnaporthe grisea. Non-pathogenic mutants have been identified that lack enzymes in the biosynthetic pathway of dihydroxynapthalene-derived melanin. These enzymes are therefore prime targets for fungicides designed to control rice blast disease. One of the enzymes identified by genetic analysis as a disease determinant is scytalone dehydratase.
The three-dimensional structure of scytalone dehydratase in complex with a competitive inhibitor has been determined at 2.9 A resolution. A novel fold, a cone-shaped alpha + beta barrel, is adopted by the monomer in this trimeric protein, burying the hydrophobic active site in its interior. The interactions of the inhibitor with the protein side chains have been identified. The similarity of the inhibitor to the substrate and the side chains involved in binding afford some insights into possible catalytic mechanisms.
These results provide a first look into the structure and catalytic residues of a non-metal dehydratase, a large class of hitherto structurally uncharacterized enzymes. It is envisaged that a detailed structural description of scytalone dehydratase will assist in the design of new inhibitors for controlling rice blast disease.
稻瘟病由致病真菌稻瘟病菌（Magnaporthe grisea）引起。已鉴定出非致病性突变体，其在二羟基萘衍生黑色素的生物合成途径中缺乏某些酶。因此，这些酶是设计用于控制稻瘟病的杀菌剂的主要靶标。通过遗传分析鉴定为疾病决定因素的一种酶是斯夸隆脱水酶。
已确定与竞争性抑制剂复合的斯夸隆脱水酶的三维结构，分辨率为2.9埃。该三聚体蛋白中的单体采用了一种新颖的折叠结构，即锥形α + β桶状结构，将疏水活性位点掩埋在其内部。已确定抑制剂与蛋白质侧链的相互作用。抑制剂与底物以及参与结合的侧链的相似性为可能的催化机制提供了一些见解。
这些结果首次揭示了一类迄今为止结构未明确的非金属脱水酶的结构和催化残基。预计对斯夸隆脱水酶的详细结构描述将有助于设计用于控制稻瘟病的新型抑制剂。
