1g0o

STRUCTURE OF TRIHYDROXYNAPHTHALENE REDUCTASE IN COMPLEX WITH NADPH AND PYROQUILON

spinqualitylabelsall models 1g0o, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1g0o is a 4 chain structure with sequence from magnaporthe_grisea Bpi 625033 magnaporthe grisea. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NDP, PYQ Related: 1doh, 1ybv, 1g0n Activity: Tetrahydroxynaphthalene reductase, with EC number 1.1.1.252 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [T4HR_MAGO7] Catalyzes the NADPH-dependent reduction of 1,3,6,8-tetrahydroxynaphthalene (T4HN) into (+)-scytalone and 1,3,8-trihydroxynaphthalene into (-)-vermelone. This enzyme is the biochemical target of several commercially important fungicides which are used to prevent blast disease in rice plants. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed BACKGROUND: Trihydroxynaphthalene reductase catalyzes two intermediate steps in the fungal melanin biosynthetic pathway. The enzyme, a typical short-chain dehydrogenase, is the biochemical target of three commercial fungicides. The fungicides bind preferentially to the NADPH form of the enzyme. RESULTS: Three X-ray structures of the Magnaporthe grisea enzyme complexed with NADPH and two commercial and one experimental fungicide were determined at 1.7 A (pyroquilon), 2.0 A (2,3-dihydro-4-nitro-1H-inden-1-one, 1), and 2.1 A (phthalide) resolutions. The chemically distinct inhibitors occupy similar space within the enzyme's active site. The three inhibitors share hydrogen bonds with the side chain hydroxyls of Ser-164 and Tyr-178 via a carbonyl oxygen (pyroquilon and 1) or via a carbonyl oxygen and a ring oxygen (phthalide). Active site residues occupy similar positions among the three structures. A buried water molecule that is hydrogen bonded to the NZ nitrogen of Lys-182 in each of the three structures likely serves to stabilize the cationic form of the residue for participation in catalysis. CONCLUSIONS: The pro S hydrogen of NADPH (which is transferred as a hydride to the enzyme's naphthol substrates) is directed toward the carbonyl carbon of the inhibitors that mimic an intermediate along the reaction coordinate. Modeling tetrahydroxynaphthalene and trihydroxynaphthalene in the active site shows steric and electrostatic repulsion between the extra hydroxyl oxygen of the former substrate and the sulfur atom of Met-283 (the C-terminal residue), which accounts, in part, for the 4-fold greater substrate specificity for trihydroxynaphthalene over tetrahydroxynaphthalene. Structures of trihydroxynaphthalene reductase-fungicide complexes: implications for structure-based design and catalysis.,Liao D, Basarab GS, Gatenby AA, Valent B, Jordan DB Structure. 2001 Jan 10;9(1):19-27. PMID:11342131 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA