PMID: 6964388Oct 1, 1982Paper

Proximity of the substrate binding site and the heme-iron catalytic site in cytochrome P-450scc

Proceedings of the National Academy of Sciences of the United States of America
J J Sheets, L E Vickery

Abstract

As an approach to "mapping" the active site of the cytochrome P-450 that catalyzes cholesterol side-chain cleavage, designated cytochrome P-450scc, we have synthesized steroid derivatives with the potential to interact with both the substrate binding site and the heme-iron catalytic site of the enzyme. The effects of these substrate analogs were studied with cytochrome P-450scc purified from bovine adrenal cortex. One derivative, 22-amino-23,24-bisnor-5-cholen-3 beta-ol, was found to be a potent inhibitor of pregnenolone formation in a reconstituted enzyme system, and a kinetic analysis of the inhibition showed that binding of the derivative is competitive with respect to cholesterol. The spectral properties of a stable complex formed between the steroidal amine and the purified cytochrome suggest that the 22-amine group coordinates directly to the heme-iron. A model for the structure of this inhibitor-enzyme complex is proposed in which the 5-androstene ring system of the steroid occupies the substrate binding site, and the amine group of the side chain occupies an axial coordination position of the Fe(III) center. This places limits on the distance between these two domains in the enzyme and offers support for proposed mechan...Continue Reading

References

Jun 7, 1976·Biochemical and Biophysical Research Communications·F LichtenbergerV Ullrich
Aug 1, 1976·Archives of Biochemistry and Biophysics·G D NordblomM J Coon
Mar 15, 1978·Biochemical and Biophysical Research Communications·J T Groves, G A McClusky
Sep 1, 1978·Archives of Biochemistry and Biophysics·H SatoM Katagiri
Apr 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·M Shikita, P F Hall
Sep 23, 1974·Biochemical and Biophysical Research Communications·A D RahimtulaR W Estabrook
Apr 15, 1972·Biochimica Et Biophysica Acta·K SuharaM Katagiri
Aug 1, 1969·Biochemistry·C R JefcoateR L Calabrese
Oct 1, 1967·European Journal of Biochemistry·E R Simpson, G S Boyd
Jan 1, 1980·Annual Review of Biochemistry·R E White, M J Coon

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Citations

Jan 1, 1991·The International Journal of Biochemistry·K IwahashiY Ichikawa
Jul 4, 1990·Journal of Steroid Biochemistry·O Olakanmi, D W Seybert
Sep 1, 1986·Microbiological Reviews·O Käppeli
Feb 15, 1988·European Journal of Biochemistry·R LangeA Bienvenüe
Oct 24, 2012·Molecular and Cellular Endocrinology·Natalia MastIrina A Pikuleva

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