HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 38, 39479-39484, September 17, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/38/39479    most recent M406838200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by He, X. Articles by de Montellano, P. R. O. Search for Related Content PubMed PubMed Citation Articles by He, X. Articles by de Montellano, P. R. O. Social Bookmarking                      What's this?

Radical Rebound Mechanism in Cytochrome P-450-catalyzed Hydroxylation of the Multifaceted Radical Clocks - and -Thujone^*

Xiang He and Paul R. Ortiz de Montellano

From the Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143-2280

-Thujone (1) and -thujone (1) were used to investigate the mechanism of hydrocarbon hydroxylation by cytochromes P-450_cam (CYP101) and P-450_BM3 (CYP102). The thujones are hydroxylated by these enzymes at various positions, but oxidation at C-4 gives rise to both rearranged and unrearranged hydroxylation products. Rearranged products result from the formation of a radical intermediate that can undergo either inversion of stereochemistry or ring opening of the adjacent cyclopropane ring. Both of these rearrangements, as well as a C-4 desaturation reaction, are observed. The ring opening clock gives oxygen rebound rates that range from 0.2 x 10¹⁰ to 2.8 x 10¹⁰ s^–1 for the different substrate and enzyme combinations. The C-4 inversion reaction provides independent confirmation of a radical intermediate. The phenol product expected if a C-4 cationic rather than radical intermediate is formed is not detected. The results are consistent with a two-state process and provide support for a radical rebound but not a hydroperoxide insertion mechanism for cytochrome P-450 hydroxylation.

Received for publication, June 18, 2004 , and in revised form, July 15, 2004.

^* This work was supported by Grant GM25515 from the National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Pharmaceutical Chemistry, University of California, 600 16th St., San Francisco, CA 94143-2280. Fax: 415-502-4728; E-mail: ortiz{at}cgl.ucsf.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?