By C.C. Reddy (Eds.)

The 1st of 2 volumes proposing present study into oxidation structures, this e-book is meant for biochemists, toxicologists, and pharmacologists. issues mentioned contain the mechanisms of organic oxidations, and peroxidases in telephone safeguard and metabolism

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Ravishankar, H. and Padmanaban, G. (1983) Arch. Biochem Biophys. 225, 4. 16-24 6. Ravishankar, H. and Padmanaban, G. (1985) /. Biol Chem 260,1588-1592 Sathyabhama, S. and Padmanaban, G. (1986) Biochemistry 25,4508-4512 8. N. and Padmanaban. G. (1987) Biochem Biophys. Res. Commun. U S , 1118-1123 9. , Jr. (1986) Ann. Rev. Pharmacol Toxicol 26,333-339 7. 10. Rangarajan. , Ravishankar, H. and Padmanaban, G. (1987) Biochem. Biophys. Res. Commun. 144,258-263 11. N. and Padmanaban, G. (1989) Proc. Natl Acad.

One summary of the proposed distribution of domains in the P-450s is shown in Figure 11 ( 2 0 ) . W. Estabrook et al 32 COS—1 c e l l s c o — t r a n s f e c t e d w i t h : pCD17a pCMVC21 hours Figure 9. The Pattern of Metabolism of Progesterone Seen when Using COS Cells Transfected with Two Different cDNAs for Bovine Adrenal P-450s. One P-450 catalyzes the 17a-hydroxylation of progesterone and the other P-450 catalyzes the 21hydroxylation of progesterone and 17a-OH progesterone. Figure 10. A Schematic Representation of the Potential Pathways of Metabolism of Progesterone Using Two Adrenal P-450s Expressed in Cotransfected COS Cells The P-450 Superfamily 33 STRUCTURAL ANALYSIS OF CYTOCHROME P-450 43 75 116/117/129 I I lili' A Β C D Ε F G Η I - II 320 365 I I ι 1 I 209/219 III I 100|| m I 200 I I 300 | 426 481 I I i | 400 | I M E M B R A N E INSERTION SIGNAL PROLINE RICH S E G M E N T C y t b 5 , KINASE INTERACTION SITE INTERNAL H A L T - T R A N S F E R S E Q U E N C E H Y P E R V A R I A B L E REGION O X Y G E N BINDING S I T E R E D U C T A S E INTERACTION SITE CONSERVED SEGMENT HEME-BINDING REGION Figure 11.

The Structure of P-450cam Showing Sites of Mutagenesis Conclusion T h e present report summarizes only a few examples of studies underway or completed on the P-450s. Clearly this multimember superfamily o f hemoproteins offers many more opportunities for new findings. Exciting results have been obtained using the expression system described ( 2 3 ) that permit the synthesis o f a single P - 4 5 0 or a combination of P-450s in cells devoid of this hemoprotein. This offers the means to establish "designer constructed" cells of predicted enzyme composition for the examination of integrated pathways o f metabolism.

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