RESUMO
The emergence of bacterial drug resistance highlights the need for new antibacterial targets. The role of protein kinases in signal transduction and cell regulation is ubiquitous. In spite of this the development of small molecule inhibitors of bacterial protein kinases has been slow, and no inhibitor has yet been successfully introduced to clinical use. In this review we focus on recent developments in inhibitors of the Histidine kinase family and pay particular attention to work on inhibiting the YycG Histidine kinase. We also highlight exciting new work in developing inhibitors for the eukaryote-like protein kinases of Mycobacterium tuberculosis including attempts to develop multi-target inhibitors.
Assuntos
Antibacterianos/metabolismo , Proteínas de Bactérias , Inibidores de Proteínas Quinases/metabolismo , Proteínas Quinases/metabolismo , Antibacterianos/química , Antibacterianos/uso terapêutico , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Desenho de Fármacos , Farmacorresistência Bacteriana Múltipla , Histidina Quinase , Humanos , Estrutura Molecular , Mycobacterium tuberculosis/enzimologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais/fisiologiaRESUMO
Protein-protein interactions create the macromolecular assemblies and sequential signaling pathways essential for cell function. Their number far exceeds the number of proteins themselves and their experimental characterization, while improving, remains relatively slow. For these reasons, novel computational methods have important roles to play in understanding the physical basis of protein interactions, and in constraining the molecular basis of their specificity. This paper discusses methods based on multiple sequence alignments of protein homologues and phylogenetic trees.
