Rational Redesign of Monoamine Oxidase A into a Dehydrogenase to Probe ROS in Cardiac Aging.

ABSTRACT: Cardiac senescence is a typical chronic frailty condition in the elderly population, and cellular aging is often associated with oxidative stress. The mitochondrial-membrane flavoenzyme monoamine oxidase A (MAO A) catalyzes the oxidative deamination of neurotransmitters, and its expression increases in aged hearts. We produced recombinant human MAO A variants at Lys305 that play a key role in O₂ reactivity leading to H₂O₂ production. The K305Q variant is as active as the wild-type enzyme, whereas K305M and K305S have 200-fold and 100-fold lower k_cat values and similar K_m. Under anaerobic conditions, K305M MAO A was normally reduced by substrate, whereas reoxidation by O₂ was much slower but could be accomplishe

SUBMITTER: Iacovino LG 

PROVIDER: S-EPMC8009472 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature