Selection of a potent inhibitor of trihydroxynaphthalene reductase by sorting disease control data.
Compounds that control rice blast, but not other crop diseases, were selected for testing as inhibitors of trihydroxynaphthalene reductase of the fungal melanin biosynthetic pathway. A potent inhibitor of the enzyme (2) (Ki = 25 nM) was identified. An X-ray structure of the enzyme-NADPH-2 complex was determined at 2.1 A resolution.
Liao
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DuPont Central Research and Development, Experimental Station, Wilmington DE, 19880, USA.
Basarab
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GS
Gatenby
A A
AA
Jordan
D B
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D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D016208:Databases, Factual; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005656:Fungal Proteins; D005658:Fungi / Q000187:drug effects*; D008543:Melanins / Q000096:biosynthesis; D008968:Molecular Conformation; D009249:NADP / Q000737:chemistry; D012275:Oryza; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010935:Plant Diseases / Q000382:microbiology*; D014961:X-Ray Diffraction
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D008543:Melanins; D009249:NADP; D010088:Oxidoreductases; C086024:tetrahydroxynaphthalene reductase; D044925:Oxidoreductases Acting on CH-CH Group Donors