The “MIDAS” platform detects protein-metabolite interactions

To help improve the discovery and characterization of elusive interactions between proteins and metabolites, researchers present MIDAS (Mass spectrometry Integrated with equilibrium Dialysis for the discovery of Allostery Systematically). According to the authors, MIDAS represents a powerful new tool to “identify, understand, and exploit previously unknown modes of metabolic regulation across the protein-metabolite interactome.” The interactions between proteins and small-molecule metabolites are among the most common and fundamental types of biological interaction and play vital roles in regulating protein functions and controlling diverse cellular processes. However, the discovery and characterization of protein-metabolite interactions (PMIs) has been sporadic and challenging. To address this, Kevin Hicks and colleagues developed the MIDAS platform, which enables the systematic discovery of elusive PMIs. Using MIDAS, Hicks et al. analyzed the interactions for 33 enzymes from human carbohydrate metabolism and 401 metabolites, which revealed 830 PMIs. Although MIDAS identified PMIs with previously known regulators, substrates, and products, the approach also allowed the authors to uncover many previously unknown PMIs from diverse metabolic pathways, including regulation of lactate dehydrogenase by ATP and long-chain acyl coenzyme A. According to the authors, this finding could be a mechanism underlying the unexpected physiological relationship between fat and carbohydrate metabolism in different tissues and could be exploited therapeutically to block aerobic glycolysis in cancers.