Model studies on the active site of cytochrome P-450 : an FeII–porphyrin carrying a strapped thiolate ligand

1982 ◽  
pp. 1266-1268 ◽  
Author(s):  
Alan R. Battersby ◽  
William Howson ◽  
Andrew D. Hamilton
Keyword(s):  
Active Site ◽  
Model Studies ◽  
Thiolate Ligand ◽  
Cytochrome P 450

scholarly journals Conversion of 19-oxo[2β-2H]androgens into oestrogens by human placental aromatase. An unexpected stereochemical outcome

1990 ◽  
Vol 268 (3) ◽  
pp. 553-561 ◽  
Author(s):  
P A Cole ◽  
C H Robinson
Keyword(s):  
Active Site ◽  
Extended Period ◽  
Direct Role ◽  
Methyl Group ◽  
Enzyme Active Site ◽  
Model Studies ◽  
The Third ◽  
Intensive Investigation ◽  
Cytochrome P 450

Aromatase is a cytochrome P-450 enzyme that catalyzes the conversion of androgens into oestrogens via sequential oxidations at the 19-methyl group. Despite intensive investigation, the mechanism of the third step, conversion of the 19-aldehydes into oestrogens, has remained unsolved. We have previously found that a pre-enolized 19-al derivative undergoes smooth aromatization in non-enzymic model studies, but the role of enolization by the enzyme in transformations of 19-oxoandrogens has not been previously investigated. The compounds 19-oxo[2 beta-2H]testosterone and 19-oxo[2 beta-2H]androstenedione have now been synthesized. Exposure of either of these compounds to microsomal aromatase, in the absence of NADPH, for an extended period led to no significant 2H loss or epimerization at C-2, leaving open the importance of an active-site base. However, in the presence of NADPH there was an unexpected substrate-dependent difference in the stereoselectivity of H loss at C-2 in the enzyme-induced aromatization of 19-oxo[2 beta-2H]-testosterone versus 19-oxo[2 beta-2H]androstenedione. The aromatization results for 17 beta-ol derivative 19-oxo[2 beta-2H]-testosterone correspond to about 1.2:1 2 beta-H/2 alpha-H loss from unlabelled 19-oxotestosterone. In contrast, aromatization results for 19-oxo[2 beta-2H]androstenedione correspond to at least 11:1 2 beta-H/2 alpha-H loss from unlabelled 19-oxoandrostenedione. This substrate-dependent stereoselectivity implies a direct role for an enzyme active-site base in 2-H removal. Furthermore, these results argue against the proposal that 2 beta-hydroxylation is the obligatory third step in aromatase action.

scholarly journals The cytochrome P-450 active site. Regiospecificity of prosthetic heme alkylation by olefins and acetylenes.

1983 ◽  
Vol 258 (7) ◽  
pp. 4202-4207 ◽  
Author(s):  
K L Kunze ◽  
B L Mangold ◽  
C Wheeler ◽  
H S Beilan ◽  
P R Ortiz de Montellano
Keyword(s):  
Active Site ◽  
Cytochrome P 450

The Topology of the Mammalian Cytochrome P-450 Active Site

1986 ◽  
pp. 77-88 ◽  
Author(s):  
Gerald T. Miwa ◽  
Anthony Y. H. Lu
Keyword(s):  
Active Site ◽  
Cytochrome P 450

The active site of cytochrome P-450 nifedipine oxidase: a model-building study

1989 ◽  
Vol 7 (4) ◽  
pp. 206-211 ◽  
Author(s):  
Gyorgy G. Ferenczy ◽  
Garrett M. Morris
Keyword(s):  
Active Site ◽  
Model Building ◽  
Cytochrome P 450

Does ?-tocopherol interact with the active site of cytochrome P-450 in liver microsomes?

1987 ◽  
Vol 103 (3) ◽  
pp. 336-339 ◽  
Author(s):  
R. I. Viner ◽  
K. N. Novikov ◽  
Yu. P. Kozlov ◽  
V. E. Kagan
Keyword(s):  
Active Site ◽  
Liver Microsomes ◽  
Cytochrome P 450
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