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This Perspective details how genome-wide association studies and metabolomics enabled the discovery of structures, bioactivities and pathways of modular metabolite biosynthesis originates from the ‘hijacking’ of conserved detoxification mechanisms by nematodes.
This perspective proposes general strategies for phase-separation-related biological studies, including proper experimental designs to validate and characterize phase-separation phenomena, connections to biological functions and some caveats to avoid common misunderstandings.
Loss of myelin causes neurological symptoms for patients with multiple sclerosis. This Perspective details how phenotypic screening has accelerated discovery efforts toward potential ‘remyelinating therapeutics’.
Emerging evidence shows that ubiquitination can occur on nonlysine residues and nonproteinaceous substrates. This perspective summarizes the recent discoveries in noncanonical ubiquitination and advocates the development of chemical biology tools for new substrate identification and mechanistic dissection.
This Perspective discussed selective partitioning behaviors of biomolecules and small molecules and proposed that understanding the chemical properties that control their interactions within the condensates would promote drug development.
New research has revealed a wealth of small molecules that target cancer-specific metabolic vulnerabilities by targeting allosteric sites. Here, a Perspective discusses how their application has provided insights into cancer metabolism and therapy.
This Perspective discusses the genetically encoded tools for measuring and manipulating metabolism, highlighting the tools that are available, guidelines for their use and key areas for future development.
Synthetic receptor signaling systems have evolved as platforms for user-controlled programming of cellular functions. This Perspective reviews these advances and defines a metrics-based engineering workflow to support future engineering efforts.
The diversity of biological pathways that are regulated by protein post-translational modification with O-GlcNAc requires community engagement to develop and apply tools to probe the biological and disease-relevant functions of these modifications.
Using extensive knowledge about the structures and mechanisms of genetically encoded fluorescent biosensors, this Perspective provides guidelines to aid and accelerate the development of an increasingly broad range of high-performance imaging tools.
This Perspective summarizes the known types of ligand-controlled ribozymes and riboswitches and discusses the reasons why allosteric ribozymes formed by fusion of RNA enzymes and RNA aptamers are rare in today’s biological systems.
This Perspective summarizes the recent advances in the structural diversity of amyloid fibrils and discusses the roles of post-translational modifications and chemical cofactors in the conformational determination of fibril polymorphs.
This Perspective introduces chemical biologists to potentially useful nanotechnologies, aims to inspire nanotechnologists to address questions relevant to chemical biology, and identifies possible opportunities for the two fields to collaborate.
The conformational cycle of a bacterial voltage-gated sodium channel as it transitions from resting to activated open to inactivated closed states can be constructed from various crystal structure snapshots.
The difficulty of antibiotic discovery posed by the double-membrane cell envelope of Gram-negative bacteria and active drug efflux requires better understanding of bacterial permeability and compound accumulation, and more diverse chemical libraries.
The Hedgehog (Hh) receptor PTCH1 uses its transporter-like function to inhibit the GPCR SMO by limiting the pool of accessible membrane cholesterol. Cholesterol acts as a ligand for SMO to activate downstream signaling.
This Perspective highlights the evolution from the use of detergents to detergent-free membrane mimetics, as well as advances in structure determination and mass spectrometry that have allowed new insights into regulation and function of membrane proteins in native-like lipid environments.
This Perspective highlights emerging themes in the inter-regulation of the genome and metabolism via chromatin, including nonenzymatic histone modifications, cofactor-promiscuous chromatin-modifying enzymes, and subnucleocytoplasmic metabolite pools.
This historical Perspective on continuous directed evolution focuses on laboratory approaches that enable greater understanding of evolving molecular populations and offer investigators tools to guide the emergence of new biomolecular systems.
This Perspective describes the chemical and biophysical principles common to all bifunctional, proximity-inducing small molecules. It also discusses the underappreciated diversity of their chemical structures and biological mechanisms.