Perspectives

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  • 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.

    • Daniel R. Squair
    • Satpal Virdee
    Perspective
  • 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.

    • Henry R. Kilgore
    • Richard A. Young
    Perspective
  • 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.

    • Daniel M. Kremer
    • Costas A. Lyssiotis
    Perspective
  • 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.

    • Janvie Manhas
    • Hailey I. Edelstein
    • Leonardo Morsut
    Perspective
  • 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.

    • Shanker S. S. Panchapakesan
    • Ronald R. Breaker
    Perspective
  • 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.

    • Ryan M. Williams
    • Shi Chen
    • Daniel A. Heller
    Perspective
  • 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.

    • William A. Catterall
    • Goragot Wisedchaisri
    • Ning Zheng
    Perspective
  • 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.

    • Shibin Zhao
    • Justyna W. Adamiak
    • Derek S. Tan
    Perspective
  • 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.

    • Arun Radhakrishnan
    • Rajat Rohatgi
    • Christian Siebold
    Perspective
  • 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.

    • Dror S. Chorev
    • Carol V. Robinson
    Perspective
  • 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.

    • Katharine L. Diehl
    • Tom W. Muir
    Perspective
  • 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.

    • Mary S. Morrison
    • Christopher J. Podracky
    • David R. Liu
    Perspective
  • 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.

    • Christopher J. Gerry
    • Stuart L. Schreiber
    Perspective
  • This Perspective focuses on the chemical basis of ferroptotic cell death, discussing the prominent role of spontaneous chemical reactions, how they depend on enzyme-catalyzed processes and how to exploit this interplay for therapeutic benefit.

    • Marcus Conrad
    • Derek A. Pratt
    Perspective
  • This Perspective summarizes recent discoveries that have laid the foundation for targeted degradation therapeutics and discusses the current state of understanding and consideration involved in developing these protein degraders.

    • Philip P. Chamberlain
    • Lawrence G. Hamann
    Perspective