In rat neuronal nitric oxide synthase, Phe1395 is positioned over the FAD isoalloxazine ring. This is replaced by Trp676 in human cytochrome P450 reductase, a tryptophan in related diflavin reductases (. methionine synthase reduc-tase andnovel reductase 1), and tyrosine inplant ferredoxin-NADP + reductase. Trp676 in human cytochrome P450 reductase is conformationallymobile, andplays akey role in enzyme reduction. Mutagenesis of Trp676 to alanine results in a functional NADH-dependent reductase. .