Enzyme Activity Assays for Protein Kinases: Strategies to Identify Active Substrates

Current Drug Discovery Technologies
Brad A Haubrich, David C Swinney

Abstract

Protein kinases are an important class of enzymes and drug targets. New opportunities to discover medicines for neglected diseases can be leveraged by the extensive kinase tools and knowledge created in targeting human kinases. A valuable tool for kinase drug discovery is an enzyme assay that measures catalytic function. The functional assay can be used to identify inhibitors, estimate affinity, characterize molecular mechanisms of action (MMOAs) and evaluate selectivity. However, establishing an enzyme assay for a new kinases requires identification of a suitable substrate. Identification of a new kinase's endogenous physiologic substrate and function can be extremely costly and time consuming. Fortunately, most kinases are promiscuous and will catalyze the phosphotransfer from ATP to alternative substrates with differing degrees of catalytic efficiency. In this manuscript we review strategies and successes in the identification of alternative substrates for kinases from organisms responsible for many of the neglected tropical diseases (NTDs) towards the goal of informing strategies to identify substrates for new kinases. Approaches for establishing a functional kinase assay include measuring auto-activation and use of generic...Continue Reading

Citations

Feb 6, 2017·The Biochemical Journal·Rossana ZaruUNKNOWN UniProt Consortium
Mar 27, 2020·International Journal of Environmental Research and Public Health·Jose ZavalaJulia E Rager
Apr 3, 2020·Acta Parasitologica·Jyotika YadavSanjay Kumar
Sep 29, 2019·Cellular and Molecular Life Sciences : CMLS·Giulia Bertolin, Marc Tramier
Oct 19, 2021·Protein Science : a Publication of the Protein Society·Manisha YadavJ Sivaraman

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