Protein-Metabolite Interactions: Discovery and Significance

Metabolites orchestrate cellular processes as either substrates, co-enzymes, inhibitors, or activators of cellular proteins such as enzymes and receptors. Although traditional biochemical and structural biology-based approaches have been successfully employed for the discovery of protein-metabolite interactions, they often fail to detect transient and low-affinity biomolecular relationships. Another limitation of these approaches is that they are performed under in vitro conditions lacking the physiological context. Recently developed mass spectrometry-based methodologies overcome both these shortcomings, and have resulted in the discovery of global protein-metabolite cellular interaction networks. Herein, we describe traditional and modern approaches for the discovery of protein-metabolite interactions, and discuss the impact of these discoveries on our understanding of cellular physiology and on drug development.

Automated summary

Metabolites play important roles in cellular processes by interacting with cellular proteins as substrates, co-enzymes, inhibitors, or activators. Traditional biochemical and structural biology-based approaches have limitations in detecting transient and low-affinity protein-metabolite interactions and lack physiological context. Mass spectrometry-based methodologies have overcome these limitations and allowed the discovery of global protein-metabolite cellular interaction networks. This article describes both traditional and modern approaches for discovering protein-metabolite interactions and discusses their impact on our understanding of cellular physiology and drug development.