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 from Magnaporthe grisea and a binary complex of the enzyme with NADPH have been determined to 2.8 A resolution. In both cases, the overall structure is preserved compared to the structure of the ternary complex of the enzyme with NADPH and an active site inhibitor. No electron density for the helix-loop-helix region comprising residues 214-244 is observed indicating structural disorder in this part of the apoenzyme and the binary complex. In the ternary complex, this region is in contact with NADPH and the inhibitor and closes off the active site. The observed increase in flexibility in the absence of the inhibitor indicates that this region acts as a lid which closes the active site upon binding of the inhibitor and, possibly the substrate, 1,3,8-trihydroxynaphthalene.
Andersson
A
A
Department of Molecular Biology, Swedish University of Agricultural Sciences, Uppsala Biomedical Center.
Jordan
D
D
Schneider
G
G
Lindqvist
Y
Y
D001203:Ascomycota / Q000201:enzymology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004583:Electrons; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism; D009249:NADP / Q000378:metabolism*; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D005656:Fungal Proteins; D011994:Recombinant Proteins; D009249:NADP; D010088:Oxidoreductases; C086024:tetrahydroxynaphthalene reductase; D044925:Oxidoreductases Acting on CH-CH Group Donors