C-Methyl isocyanide as an NMR probe for cytochrome P450 active sites

The cytochromes P450 (CYPs) play a central role in many biologically important oxidation reactions, including the metabolism of drugs and other xenobiotic compounds. Because they are often assayed as both drug targets and anti-targets, any tools that provide: (a) confirmation of active site binding...

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Bibliographic Details
Published inJournal of biomolecular NMR Vol. 43; no. 3; pp. 171 - 178
Main Authors McCullough, Christopher R, Pullela, Phani Kumar, Im, Sang-Choul, Waskell, Lucy, Sem, Daniel S
Format Journal Article
LanguageEnglish
Published Dordrecht : Springer Netherlands 2009
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Summary:The cytochromes P450 (CYPs) play a central role in many biologically important oxidation reactions, including the metabolism of drugs and other xenobiotic compounds. Because they are often assayed as both drug targets and anti-targets, any tools that provide: (a) confirmation of active site binding and (b) structural data, would be of great utility, especially if data could be obtained in reasonably high throughput. To this end, we have developed an analog of the promiscuous heme ligand, cyanide, with a ¹³CH₃-reporter attached. This ¹³C-methyl isocyanide ligand binds to bacterial (P450cam) and membrane-bound mammalian (CYP2B4) CYPs. It can be used in a rapid 1D experiment to identify binders, and provides a qualitative measure of structural changes in the active site.
Bibliography:http://dx.doi.org/10.1007/s10858-009-9300-8
ISSN:0925-2738
1573-5001
DOI:10.1007/s10858-009-9300-8