A purified polypeptide includes an NADPH oxidase cytosolic cofactor polypeptide NOXA1 or p67.sup.phox having a C-terminal SH3 domain insertion mutation of at least three consecutive amino acids positioned between PEDL (SEQ ID NO: 35) and GIFPK (SEQ ID NO: 34) motifs of said SH3 domain so as to reduce activity of the purified polypeptide relative to the wild-type cofactor polypeptide. A process for treating, inhibiting, or prophylactically preventing a disease associated with the overproduction of reactive oxygen species involving NOXn where n is 1-4 inclusive includes the administration of a therapeutically effective amount with a purified polypeptide to a subject tissue that is overproducing reactive oxygen species through a NOXn pathway.