Journal
CHEMBIOCHEM
Volume -, Issue -, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.202200755
Keywords
allostery; cellular physiology; drug development; mass spectrometry; photo-crosslinking; protein function
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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.
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.
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