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Updated: Aug 3, 2026
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Microwave-assisted Intramolecular Dehydrogenative Diels-Alder Reactions for the Synthesis of Functionalized Naphthalenes/Solvatochromic Dyes
Published on: April 1, 2013
Structures of trihydroxynaphthalene reductase-fungicide complexes: implications for structure-based design and
D Liao1, G S Basarab, A A Gatenby
1DuPont Central Research and Development Experimental Station, Wilmington, DE 19880, USA. der-ling.liao@usa.dupont.com
Structure (London, England : 1993)
|May 9, 2001
Summary
Fungicide binding to trihydroxynaphthalene reductase was studied using X-ray crystallography. Inhibitors occupy a conserved active site, guiding NADPH hydride transfer and explaining substrate specificity in fungal melanin biosynthesis.
Area of Science:
- Biochemistry
- Structural Biology
- Mycology
Background:
- Trihydroxynaphthalene reductase is key in fungal melanin production.
- It's a short-chain dehydrogenase targeted by fungicides.
- Fungicides bind to the NADPH form of the enzyme.
Purpose of the Study:
- Determine the X-ray structures of Magnaporthe grisea trihydroxynaphthalene reductase.
- Analyze the binding of NADPH and three distinct fungicides.
- Understand the structural basis for fungicide action and substrate specificity.
Main Methods:
- X-ray crystallography
- Enzyme kinetics
- Structural analysis of enzyme-inhibitor complexes
Main Results:
- Three X-ray structures were solved at high resolution (1.7–2.1 Å) with NADPH and fungicides (pyroquilon, compound 1, phthalide).
- All inhibitors bind to a conserved active site, forming hydrogen bonds with Ser-164 and Tyr-178.
- A buried water molecule stabilizes Lys-182, crucial for catalysis.
Conclusions:
- Inhibitors mimic reaction intermediates, directing NADPH hydride transfer.
- Steric and electrostatic interactions explain the enzyme's preference for trihydroxynaphthalene over tetrahydroxynaphthalene.
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