ArticleScientific reports2022
Brunner syndrome caused by point mutation explained by multiscale simulation of enzyme reaction.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Genotype-Driven Diagnosis Enables Targeted Pharmacological Treatment in Brunner Syndrome: A Novel Splice-SiteInternational journal of molecular sciences · 2026Review
- Efficient Multistate Free-Energy Calculations with QM/MM Accuracy Using Replica-Exchange Enveloping Distribution Sampling.The journal of physical chemistry. B · 2025Article
- Investigation of Electrostatic Effects on Enyzme Catalysis: Insights from Computational Simulations of Monoamine Oxidase A Pathological Variants Leading to the Brunner Syndrome.Journal of chemical information and modeling · 2025Article
- A general approach for activity-based protein profiling of oxidoreductases with redox-differentiated diarylhalonium warheads.Chemical science · 2025Article
- Article
- Monitoring Enzyme Activity Using Near-Infrared Fluorescent Single-Walled Carbon Nanotubes.ACS sensors · 2024Review
- Inhibitory mechanism of vortioxetine on CYP450 enzymes in human and rat liver microsomes.Frontiers in pharmacology · 2023Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brunner syndrome is a disorder characterized by intellectual disability and impulsive, aggressive behavior associated with deficient function of the monoamine oxidase A (MAO-A) enzyme. These symptoms (along with particularly high serotonin levels) have been reported in patients with two missense variants in MAO-A (p.R45W and p.E446K). Herein, we report molecular simulations of the rate-limiting step of MAO-A-catalyzed serotonin degradation for these variants. We found that the R45W mutation causes a 6000-fold slowdown of enzymatic function, whereas the E446K mutation causes a 450-fold reduction of serotonin degradation rate, both of which are practically equivalent to a gene knockout. In addition, we thoroughly compared the influence of enzyme electrostatics on the catalytic function of both the wild type MAO-A and the p.R45W variant relative to the wild type enzyme, revealing that the mutation represents a significant electrostatic perturbation that contributes to the barrier increase. Understanding genetic disorders is closely linked to understanding the associated chemical mechanisms, and our research represents a novel attempt to bridge the gap between clinical genetics and the underlying chemical physics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.