Revealing Monoamine Oxidase B Catalytic Mechanisms by Means of the Quantum Chemical Cluster Approach
| Autor: | Cristian Celis-Barros, Gerald Zapata-Torres, Angélica Fierro, J. Cristian Salgado, Germán Barriga-González |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Benzylamines Stereochemistry General Chemical Engineering Amino Acid Motifs Library and Information Sciences chemistry.chemical_compound Benzylamine Phenethylamines Humans Molecule Reactivity (chemistry) Monoamine Oxidase biology Chemistry Hydride Water Active site Oxidative deamination General Chemistry Transition state Computer Science Applications Kinetics Biocatalysis biology.protein Quantum Theory Thermodynamics Monoamine oxidase B |
| Zdroj: | Journal of Chemical Information and Modeling. 55:1349-1360 |
| ISSN: | 1549-960X 1549-9596 |
| Popis: | Two of the possible catalytic mechanisms for neurotransmitter oxidative deamination by monoamine oxidase B (MAO B), namely, polar nucleophilic and hydride transfer, were addressed in order to comprehend the nature of their rate-determining step. The Quantum Chemical Cluster Approach was used to obtain transition states of MAO B complexed with phenylethylamine (PEA), benzylamine (BA), and p-nitrobenzylamine (NBA). The choice of these amines relies on their importance to address MAO B catalytic mechanisms so as to help us to answer questions such as why BA is a better substrate than NBA or how para-substitution affects substrate's reactivity. Transition states were later validated by comparison with the experimental free energy barriers. From a theoretical point of view, and according to the our reported transition states, their calculated barriers and structural and orbital differences obtained by us among these compounds, we propose that good substrates such as BA and PEA might follow the hydride transfer pathway while poor substrates such as NBA prefer the polar nucleophilic mechanism, which might suggest that MAO B can act by both mechanisms. The low free energy barriers for BA and PEA reflect the preference that MAO B has for hydride transfer over the polar nucleophilic mechanism when catalyzing the oxidative deamination of neurotransmitters. |
| Databáze: | OpenAIRE |
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