Investigation of Electrostatic Effects on Enyzme Catalysis: Insights from Computational Simulations of Monoamine Oxidase A Pathological Variants Leading to the Brunner Syndrome.

ABSTRACT: Brunner syndrome is a rare genetic disorder characterized by impulsive aggressiveness and intellectual disability, which is linked to impaired function of the monoamine oxidase A (MAO-A) enzyme. Patients with specific point mutations in the MAOA gene have been reported to exhibit these symptoms, along with notably elevated serotonin levels, which suggest a decreased catalytic performance of the mutated MAO-A enzymes. In this study, we present multiscale molecular simulations focusing on the rate-limiting step of MAO-A-catalyzed serotonin degradation for the C266F and V244I variants that are reportedly associated with pathologies characteristic of the Brunner syndrome. We found that the C266F mutation causes an approximately 18,000-fold slowdown of enzymatic function, which is equiva

SUBMITTER: Rajic M 

PROVIDER: S-EPMC12004519 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature