Role of a hydrophobic polypeptide in the Nterminal region of NADPH-cytochrome P-450 reductase in complex formation with P-450LM." Biochem Biophys Res Commun 91(4

SUMMARY: Detergent-solubilired liver microsomal NADPH-cytochrome P-450 reductase is known to retain the ability to catalyze electron transfer to cyto-chrome P-450, whereas the trypsin-solubilized reductase does not. In the pre-sent study, treatment of the highly purified detergent-solubilized rabbit liver enzyme (m.w. 77,700) with trypsin was shown to yield a small peptide (m.w. 6,100) as well as the large peptide (m.w. 71,200) which retains the flavin pros-thetfc groups. The small peptide, which is hydrophobic in nature as shown by its amino acid composition and solubility properties, is apparently the moiety in the native reductase involved in binding to cytochrome P-450 and to the mi-crosomal membrane. The C-terminalaminoacid sequences of the native reductaseand large fragment are identical [-Trp-(Leu, Val)-Asp-Ser-COOH], thereby indica-ting that the hydrophobic peptide is located in the N-terminal region of the enzyme. After the liver microsomal hydroxylation system was reconstituted from de-tergent-solubilized cytochrome P-450 and NADPH-cytochrome P-450 reductase i