Posttranslational modification by an isolevuglandin diminishes activity of the mitochondrial cytochrome P450 27A1.

ABSTRACT: Posttranslational modification by isolevuglandins (isoLGs), arachidonate oxidation products, is an important yet understudied process associated with altered protein properties. This type of modification is detected in cytochrome P450 27A1 (CYP27A1), a multifunction enzyme expressed in almost every cell and involved in the metabolism of cholesterol and other sterols. Previously, the CYP27A1 Lys(358)-isoLG adduct was found in human retina afflicted with age-related macular degeneration. Yet, the effect of Lys(358) modification on enzyme activity was not investigated. Herein, we characterized catalytic properties of Lys(358) as well as Lys(476) CYP27A1 mutants before and after isoLG treatment and quantified the extent of modification by multiple reaction monitoring. The K358R mutant was less

SUBMITTER: Charvet CD 

PROVIDER: S-EPMC3622334 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature