cys-->ser mutations in ch-human dihydropteridine reductase.

The cDNA sequence of dihydropteridine reductase (DHPR) showed that the enzyme has four cysteine residues.1,2 These are cys26, cys85, cys104 and cys161. Evidence from titration experiments of human and rat DHPR with thiol reagents and platinum II complexes suggested that when one of the cysteines was masked by addition of NADH then it did not react with these reagents and the enzyme was protected from inactivation.3,4 In order to see if one of these cysteine residues was the proton source for the enzymic reduction of quinonoid dihydropterin substrates, we investigated the effect of replacing the cysteine residues by serine residues, which are weaker acids, and we examined the kinetics of the mutant proteins.