title: Crystal structure of rat liver dihydropteridine reductase.
abstract: The structure of a binary complex of dihydropteridine reductase [DHPR; NAD(P)H:6,7-dihydropteridine oxidoreductase, EC 1.6.99.7] with its cofactor, NADH, has been solved and refined to a final R factor of 15.4% by using 2.3 A diffraction data. DHPR is an alpha/beta protein with a Rossmann-type dinucleotide fold for NADH binding. Insertion of an extra threonine residue in the human enzyme is associated with severe symptoms of a variant form of phenylketonuria and maps to a tightly linked sequence of secondary-structural elements near the dimer interface. Dimerization is mediated by a four-helix bundle motif (two helices from each protomer) having an unusual right-handed twist. DHPR is structurally and mechanistically distinct from dihydrofolate reductase, appearing to more closely resemble certain nicotinamide dinucleotide-requiring flavin-dependent enzymes, such as glutathione reductase.
authors.affiliation: Department of Biology, University of California, San Diego, La Jolla 92093-0317.
authors.forename: K I
authors.initials: KI
authors.lastname: Varughese
authors.forename: M M
authors.initials: MM
authors.lastname: Skinner
authors.forename: J M
authors.initials: JM
authors.lastname: Whiteley
authors.forename: D A
authors.initials: DA
authors.lastname: Matthews
authors.forename: N H
authors.initials: NH
authors.lastname: Xuong
mesh_terms: D000818:Animals; D001665:Binding Sites; D003461:Crystallography; D004093:Dihydropteridine Reductase / Q000648:ultrastructure*; D008099:Liver / Q000201:enzymology*; D008958:Models, Molecular; D011487:Protein Conformation; D051381:Rats; D014961:X-Ray Diffraction
chemical_list: D004093:Dihydropteridine Reductase