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Commun Biol ; 3(1): 263, 2020 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-32451394

RESUMO

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.


Assuntos
Agaricales/efeitos dos fármacos , Agaricales/genética , Fungicidas Industriais/farmacologia , Proteínas Mitocondriais/genética , Oxirredutases/genética , Proteínas de Plantas/genética , Terpenos/farmacologia , Agaricales/química , Agaricales/enzimologia , Relação Dose-Resposta a Droga , Cinética , Proteínas Mitocondriais/antagonistas & inibidores , Proteínas Mitocondriais/química , Proteínas Mitocondriais/metabolismo , Oxirredutases/antagonistas & inibidores , Oxirredutases/química , Oxirredutases/metabolismo , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
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