13C-Methyl isocyanide as an NMR probe for cytochrome P450 active site

Authors

Christopher R McCullough, Marquette University
Phani Kumar Pullela, Marquette University
Sang-Choul Im, University of Michigan - Ann ArborFollow
Lucy Waskell, University of Michigan - Ann ArborFollow
Daniel S. Sem, Marquette UniversityFollow

Document Type

Article

Publication Date

2009

Source Publication

Journal of Biomolecular NMR

Source ISSN

0925-2738

Abstract

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.

Comments

Accepted version. Journal of Biomolecular NMR, Volume 43, No.3, pp 171-178 (2009). DOI. © 2009 Springer. Used with permission.

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Recommended Citation

McCullough, Christopher R; Pullela, Phani Kumar; Im, Sang-Choul; Waskell, Lucy; and Sem, Daniel S., "13C-Methyl isocyanide as an NMR probe for cytochrome P450 active site" (2009). Chemistry Faculty Research and Publications. 85.
https://epublications.marquette.edu/chem_fac/85