Crystal structure of rat liver dihydropteridine reductase.
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.
Varughese
K I
KI
Department of Biology, University of California, San Diego, La Jolla 92093-0317.
Skinner
M M
MM
Whiteley
J M
JM
Matthews
D A
DA
Xuong
N H
NH
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
D004093:Dihydropteridine Reductase