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. 1992 Jul 1;89(13):6080–6084. doi: 10.1073/pnas.89.13.6080

Crystal structure of rat liver dihydropteridine reductase.

K I Varughese 1, M M Skinner 1, J M Whiteley 1, D A Matthews 1, N H Xuong 1
PMCID: PMC49441  PMID: 1631094

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.

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Selected References

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