REGULAR ARTICLEMechanism-Based Inactivation of Cytochrome P450 2B1 by 9-Ethynylphenanthrene
References (0)
Cited by (51)
Targeting of the highly conserved threonine 302 residue of cytochromes P450 2B family during mechanism-based inactivation by aryl acetylenes
2011, Archives of Biochemistry and BiophysicsCitation Excerpt :MALDI-MS analyses of the [3H]9EPh-labeled peptides following cleavage with CNBr indicated the addition of phenanthrylacetyl group to the peptide. Peptide mapping of the pepsin-digest demonstrated that the radiolabeled peptide 294–307 was the site of covalent modification [30,31]. The functional importance of Thr302 in the inactivation of CYP2B4 by 2EN was confirmed when the T302A variant was shown to exhibit a significantly slower rate of inactivation by 2EN compared to CYP2B4 WT [32].
Inhibition of CYP2B4 by the mechanism-based inhibitor 2-ethynylnaphthalene: Inhibitory potential of 2EN is dependent on the size of the substrate
2007, Archives of Biochemistry and BiophysicsCitation Excerpt :As an initial experiment, the effect of 2EN on 7-pentoxyresorufin-O-dealkylation (PROD) was examined (Fig. 1a). Preincubation with 2EN for 10 min led to an 85% decrease in PROD activity, a response typically observed with mechanism-based inhibitors [2,7,8,25]. However, a significant amount of inhibition of PROD was also observed without 2EN preincubation, which is consistent with a simple reversible interaction of 2EN with the enzyme.
The mechanism-based inactivation of P450 2B4 by tert-butyl 1-methyl-2-propynyl ether: Structural determination of the adducts to the P450 heme
2004, Archives of Biochemistry and BiophysicsCitation Excerpt :Adduct C gives rise to signals with a slight downfield shift compared to adduct B. For example, the tert-butyl group has a chemical shift of −1.17 ppm compared to −0.91 ppm for adduct B (Fig. 4F). A number of acetylenic compounds have been identified as mechanism-based inactivators of various P450 2B enzymes [7,13,15,16,31–33]. The mechanism, as well as the rate of inactivation, differs significantly among the P450s and between different inactivators.
Mechanistic studies of cytochrome P450 2B1 inactivation by xanthates
2000, Archives of Biochemistry and BiophysicsSymptomatic and neuroprotective properties of the aliphatic propargylamines
1999, Mechanisms of Ageing and DevelopmentAcetylenes: cytochrome P450 oxidation and mechanism-based enzyme inactivation
2019, Drug Metabolism Reviews