Defining the Structural Consequences of Mechanism-Based Inactivation of Mammalian Cytochrome P450 2B4 Using Resonance Raman Spectroscopy
Document Type
Article
Language
eng
Format of Original
2 p.
Publication Date
2-2010
Publisher
American Chemical Society
Source Publication
Journal of the American Chemical Society
Source ISSN
0002-7863
Original Item ID
DOI: 10.1021/ja910276s
Abstract
In view of the potent oxidizing strength of cytochrome P450 intermediates, it is not surprising that certain substrates can give rise to reactive species capable of attacking the heme or critical distal-pocket protein residues to irreversibly modify the enzyme in a process known as mechanism-based (MB) inactivation, a result that can have serious physiological consequences leading to adverse drug−drug interactions and toxicity. While methods exist to document the attachment of these substrate fragments, it is more difficult to gain insight into the structural basis for the altered functional properties of these modified enzymes. In response to this pressing need to better understand MB inhibition, we here report the first application of resonance Raman spectroscopy to study the inactivation of a truncated form of mammalian CYP2B4 by the acetylenic inhibitor 4-(tert-butyl)phenylacetylene, whose activated form is known to attach to the distal-pocket T302 residue of CYP2B4.
Recommended Citation
Mak, Piotr J.; Zhang, Haoming; Hollenberg, Paul F.; and Kincaid, James R., "Defining the Structural Consequences of Mechanism-Based Inactivation of Mammalian Cytochrome P450 2B4 Using Resonance Raman Spectroscopy" (2010). Chemistry Faculty Research and Publications. 366.
https://epublications.marquette.edu/chem_fac/366
Comments
Accepted version. Journal of the American Chemical Society, Vol. 132, No. 5 (February 2010): 1494-1495. DOI. © 2010 American Chemical Society. Used with permission.