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Commun Biol ; 3(1): 263, 2020 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-32451394

RESUMEN

Moniliophthora perniciosa is a fungal pathogen and causal agent of the witches' broom disease of cocoa, a threat to the chocolate industry and to the economic and social security in cocoa-planting countries. The membrane-bound enzyme alternative oxidase (MpAOX) is crucial for pathogen survival; however a lack of information on the biochemical properties of MpAOX hinders the development of novel fungicides. In this study, we purified and characterised recombinant MpAOX in dose-response assays with activators and inhibitors, followed by a kinetic characterization both in an aqueous environment and in physiologically-relevant proteoliposomes. We present structure-activity relationships of AOX inhibitors such as colletochlorin B and analogues which, aided by an MpAOX structural model, indicates key residues for protein-inhibitor interaction. We also discuss the importance of the correct hydrophobic environment for MpAOX enzymatic activity. We envisage that such results will guide the future development of AOX-targeting antifungal agents against M. perniciosa, an important outcome for the chocolate industry.


Asunto(s)
Agaricales/efectos de los fármacos , Agaricales/genética , Fungicidas Industriales/farmacología , Proteínas Mitocondriales/genética , Oxidorreductasas/genética , Proteínas de Plantas/genética , Terpenos/farmacología , Agaricales/química , Agaricales/enzimología , Relación Dosis-Respuesta a Droga , Cinética , Proteínas Mitocondriales/antagonistas & inhibidores , Proteínas Mitocondriales/química , Proteínas Mitocondriales/metabolismo , Oxidorreductasas/antagonistas & inhibidores , Oxidorreductasas/química , Oxidorreductasas/metabolismo , Proteínas de Plantas/antagonistas & inhibidores , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
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