STRUCTURAL AND MECHANISTIC CHARACTERISTICS OF DIHYDROPTERIDINE REDUCTASE - A MEMBER OF THE TYR-(XAA)(3)-LYS-CONTAINING FAMILY OF REDUCTASESAND DEHYDROGENASES

Dihydropteridine reductase (EC 1.6.99.7) is a member of the recently i dentified family of proteins known as short chain dehydrogenases. When the x-ray structure of dihydropteridine reductase is correlated with conserved amino acid sequences characteristic of this enzyme class, tw o important common structural regions can be identified. One is close to the protein N terminus and serves as the cofactor binding site, whi le a second conserved feature makes up the inner surface of an alpha-h elix in which a tyrosine side chain is positioned in close proximity t o a lysine residue four residues downstream in the sequence. The main function of this Tyr-Lys couple may be to facilitate tyrosine hydroxyl group participation in proton transfer. Thus, it appears that there i s a distinctive common mechanism for this group of short-chain or pyri dine dinucleotide-dependent oxidoreductases that is different from the ir higher molecular weight counterparts.