1. Phosphonium compounds as new and specific inhibitors of bovine serum amine oxidase
- Author
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Michele Lunelli, Adelio Rigo, Marina Scarpa, and Maria Luisa Di Paolo
- Subjects
Serum ,Amine oxidase ,Stereochemistry ,phosphonium compounds ,competitive inhibition ,enzyme kinetics ,amine oxidases ,Structure-function relationships ,Binding, Competitive ,Sensitivity and Specificity ,Biochemistry ,Substrate Specificity ,Structure-Activity Relationship ,chemistry.chemical_compound ,Onium Compounds ,Organophosphorus Compounds ,Animals ,Structure–activity relationship ,Phosphonium ,Enzyme Inhibitors ,Bovine serum albumin ,Binding site ,Molecular Biology ,Binding Sites ,biology ,Chemistry ,Amine oxidase (copper-containing) ,Active site ,Onium compound ,Cell Biology ,Hydrogen-Ion Concentration ,Kinetics ,biology.protein ,Cattle ,Amine Oxidase (Copper-Containing) ,Hydrophobic and Hydrophilic Interactions ,Research Article - Abstract
TPP+ (tetraphenylphosphonium ion) and its analogues were found to act as powerful competitive inhibitors of BSAO (bovine serum amine oxidase). The binding of this new class of inhibitors to BSAO was characterized by kinetic measurements. TPP+ can bind to the BSAO active site by hydrophobic and by coulombian interactions. The binding probably occurs in the region of the ‘cation-binding site’[Di Paolo, Scarpa, Corazza, Stevanato and Rigo (2002) Biophys. J. 83, 2231–2239]. Under physiological conditions, the association constant of TPP+ for this site is higher than 106 M−1, the change of enthalpy being the main free-energy term controlling binding. Analysis of the relationships between substrate structure and extent of inhibition by TPP+ reveals some new molecular features of the BSAO active site.
- Published
- 2004
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