A FLEXIBLE LID CONTROLS ACCESS TO THE ACTIVE-SITE IN 1,3,8-TRIHYDROXYNAPHTHALENE REDUCTASE

The crystal structures of apo-1,3,8-trihydroxynaphthalene reductase fr om Magnaporthe grisea and a binary complex of the enzyme with NADPH ha ve been determined to 2.8 Angstrom resolution. In both cases, the over all structure is preserved compared to the structure of the ternary co mplex of the enzyme with NADPH and an active site inhibitor. No electr on density for the helix-loop-helix region comprising residues 214-244 is observed indicating structural disorder in this part of the apoenz yme and the binary complex. In the ternary complex, this region is in contact with NADPH and the inhibitor and closes off the active site. T he observed increase in flexibility in the absence of the inhibitor in dicates that this region acts as a lid which closes the active site up on binding of the inhibitor and, possibly the substrate, 1,3,8-trihydr oxynaphthalene.