cDNA sequence of adrenodoxin reductase: Identification of NADP‐binding sites in oxidoreductases

Adrenodoxin reductase is an NADP dependent flavoenzyme which functions as the reductase of mitochondrial P 450 systems. We sequenced two adrenodoxin reductase cDNAs isolated from a bovine adrenal cortex cDNA library. The deduced amino acid sequence shows no similarity to the sequence of the microsomal P 450 systems or other known protein sequences. Nonetheless, by sequence analysis and comparisons with known sequences of dinucleotide‐binding folds of two NADP‐binding flavoenzymes, two regions of adrenodoxin reductase sequence were identified as the FAD‐ and NADP‐binding sites. These analyses revealed a consensus sequence for the NADP‐binding dinucleotide fold (GXGXXAXXXAXXXXXXG, in one‐letter amino acid code) that differs from FAD and NAD‐binding dinucleotide‐fold sequences. In the data base of protein sequences, the NADP‐binding‐site sequence appears solely in NADP‐dependent enzymes, the binding sites of which were not known to date. Thus, this sequence may be used for identification of a certain type of NADP‐binding site of enzymes that show no significant sequence similarity.