caa a22 4500 475743814 CHVBK 20180406123507.0 cr unu---uuuuu 170329e20000101xx s 000 0 eng 10.1023/A:1007038724874 doi (NATIONALLICENCE)springer-10.1023/A:1007038724874 Synthetic Peptide Mimics of a Predicted Topographical Interaction Surface: The Cytochrome P450 2B1 Recognition Domain for NADPH-Cytochrome P450 Reductase [Elektronische Daten] [Yoshiaki Omata, Renke Dai, Stanley Smith, Richard Robinson, Fred Friedman] In order to identify the cytochrome P450-binding domain for NADPH-cytochrome P450 reductase, synthetic peptide mimics of predicted surface regions of rat cytochrome P450 2B1 were constructed and evaluated for inhibition of the P450-reductase interaction. A peptide corresponding to residues 116-134, which includes the C helix, completely inhibited reductase-mediated benzphetamine demethylation by purified P450 2B1. Replacement of Arg-125 by Glu yielded a noninhibitory peptide, suggesting that this residue significantly contributes to the reductase-P450 interaction. Additional P450 peptides were prepared which correspond to combinations of regions distant in primary sequence, but predicted to be spatially proximate. A peptide derived from segments of the C and L helices was a more potent inhibitor than peptides derived from either segment alone. This topographically designed peptide not only inhibited P450 2B1 in its purified form, but also when membrane-bound in rat liver microsomes. The peptide also inhibited microsomal aryl hydrocarbon hydroxylase, aniline hydroxylase, and erythromycin demethylase activities derived from other P450s. These results indicate that the C and L helices contribute to a reductase-binding site common to multiple P450s, and present a peptide mimic for this region that is useful for inhibition of P450-mediated microsomal activities. Plenum Publishing Corporation, 2000 Protein structure nationallicence protein-protein interactions nationallicence peptide mimics nationallicence cytochrome P450 nationallicence drug metabolism nationallicence Omata Yoshiaki Laboratory of Molecular Carcinogenesis, National Cancer Institute, 20892, Bethesda, Maryland aut Dai Renke Laboratory of Molecular Carcinogenesis, National Cancer Institute, 20892, Bethesda, Maryland aut Smith Stanley Laboratory of Molecular Carcinogenesis, National Cancer Institute, 20892, Bethesda, Maryland aut Robinson Richard Laboratory of Molecular Carcinogenesis, National Cancer Institute, 20892, Bethesda, Maryland aut Friedman Fred Laboratory of Molecular Carcinogenesis, National Cancer Institute, 20892, Bethesda, Maryland aut Journal of Protein Chemistry Kluwer Academic Publishers-Plenum Publishers 19/1(2000-01-01), 23-32 0277-8033 19:1<23 2000 19 10930 https://doi.org/10.1023/A:1007038724874 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1007038724874 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Omata Yoshiaki Laboratory of Molecular Carcinogenesis, National Cancer Institute, 20892, Bethesda, Maryland aut NATIONALLICENCE 700 1- Dai Renke Laboratory of Molecular Carcinogenesis, National Cancer Institute, 20892, Bethesda, Maryland aut NATIONALLICENCE 700 1- Smith Stanley Laboratory of Molecular Carcinogenesis, National Cancer Institute, 20892, Bethesda, Maryland aut NATIONALLICENCE 700 1- Robinson Richard Laboratory of Molecular Carcinogenesis, National Cancer Institute, 20892, Bethesda, Maryland aut NATIONALLICENCE 700 1- Friedman Fred Laboratory of Molecular Carcinogenesis, National Cancer Institute, 20892, Bethesda, Maryland aut NATIONALLICENCE 773 0- Journal of Protein Chemistry Kluwer Academic Publishers-Plenum Publishers 19/1(2000-01-01), 23-32 0277-8033 19:1<23 2000 19 10930 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer