Modulation of heme peroxo nucleophilicities with axial ligands reveal key insights into the mechanistic landscape of nitric oxide synthase.

ABSTRACT: Mid-valent heme-oxygen intermediates are central to a medley of pivotal physiological transformations in humans, and such systems are increasingly becoming more relevant therapeutic targets for challenging disease conditions. Nonetheless, precise mechanistic details pertaining to mid-valent heme intermediates as well as key structure-activity relationships remain enigmatic. To this end, this study strives to describe the influence of heme proximal ligation on the nucleophilic reactivity patterns of heme peroxo intermediates. A functional model system in which organic oxime substrates are used as N-hydroxy-l-arginine mimics reproduces the second mechanistic step of nitric oxide synthase. Our findings reveal that axial ligation of heme peroxo adducts escalates the rates of nucleophili

SUBMITTER: Rajapakse S 

PROVIDER: S-EPMC12062894 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature