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Studies on Regioselective Binding Mode of Steroid Molecules in Homology Modeled Cytochrome P450-2C11

Hamed I. Ali¹, Morio Yamada², Hukihisa Fujita³ & Eiichi Akaho⁴

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1. Faculty of Pharmacy, Helwan University
2. Department of Chemistry, Hyogo College of Medicine
3. Liberal Arts Center, Hyogo University of Health Sciences
4. Faculty of Pharmaceutical Sciences, Kobe Gakuin University

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Document Type:

Manuscript

Date:

Received 03 August 2009 05:39 UTC; Posted 03 August 2009

Subjects:

Chemistry, Bioinformatics

Tags:

• receptor
• docking
• steroid
• cytochorme p450
• hydroxylation
• regioselective binding mode
• structure

Abstract:

In this study, we investigated the regioselective binding mode of steroid molecules and structure requirements for steroid molecules for 16α-hydroxylation by Cytochrome P450-2C11. Docking study by using the homology Cytochrome P450-2C11 indicated that 16α-hydroxylation is favored with steroidal molecules possessing the following components, 1) a bent A-B ring configuration (5β-reduced), 2) C-3α-hydroxyl group, 3) C-17β-acetyl group, and 4) methyl group at both the C-18 and C-19. These respective steroid components requirements such as A-B ring configuration and functional groups at C-3 and C-17 were defined as the inhibitory contribution factor. Overall results by rat CYP2C11 revealed that steroidal structure requirements resulted in causing an effective inhibition of [³H]progesterone 16α-hydroxylation by the adult male rat liver microsome. As far as docking of homology modeled CYP2C11 against investigated steroids is concerned, they are docked at the active site superimposed with flurbiprofen. It was also found that the distance between heme iron and C16α-H was between 4 to 6 Å and that the related angle was in the range of 180±45°.

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This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Ali, Hamed, Yamada, Morio, Fujita, Hukihisa, and Akaho, Eiichi. Studies on Regioselective Binding Mode of Steroid Molecules in Homology Modeled Cytochrome P450-2C11. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2009.3541.1> (2009)

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