Featured
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Article
| Open Access
Targeted protein degradation via intramolecular bivalent glues
Studies using genetic screening, biophysical characterization and structural reconstitution elucidate the mechanism of action and enable rational design of a new class of functional compounds that glue target proteins to E3 ligases via intramolecularly bridging two domains to enhance intrinsic protein–protein interactions and promote target ubiquitination and degradation.
- Oliver Hsia
- , Matthias Hinterndorfer
- & Alessio Ciulli
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Article |
Tracking chromatin state changes using nanoscale photo-proximity labelling
A proximity labelling-based approach for mapping nuclear protein–protein interactions is described that could advance epigenetic drug discovery.
- Ciaran P. Seath
- , Antony J. Burton
- & Tom W. Muir
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Article |
The E3 ligase adapter cereblon targets the C-terminal cyclic imide degron
C-terminal cyclic imides are physiological degrons that enable the ubiquitin E3 ligase adapter protein cereblon to target substrates for degradation.
- Saki Ichikawa
- , Hope A. Flaxman
- & Christina M. Woo
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Article
| Open Access
Mechanism-based traps enable protease and hydrolase substrate discovery
Light-activated trapping is used in a mechanism-based assay to capture and identify substrates of protein hydrolases.
- Shan Tang
- , Adam T. Beattie
- & Jason W. Chin
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Article |
Lysosome-targeting chimaeras for degradation of extracellular proteins
Lysosome-targeting chimaeras—in which a small molecule or antibody is connected to a glycopeptide ligand to form a conjugate that can bind a cell-surface lysosome-shuttling receptor and a protein target—are used to achieve the targeted degradation of extracellular and membrane proteins.
- Steven M. Banik
- , Kayvon Pedram
- & Carolyn R. Bertozzi
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Letter |
Discovery of a pathway for terminal-alkyne amino acid biosynthesis
Microbial generation of a terminal-alkyne-containing amino acid can be encoded into E. coli and provides the potential for in vivo generation of proteins and natural products for click chemistry.
- J. A. Marchand
- , M. E. Neugebauer
- & M. C. Y. Chang
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Letter |
Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity
Non-lysine ubiquitination activity of the E3 ubiquitin ligase MYCBP2 is identified by activity-based profiling; biochemical and structural analysis of MYCBP2 suggests the basis for its mechanism and specificity.
- Kuan-Chuan Pao
- , Nicola T. Wood
- & Satpal Virdee
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Letter |
Proteome-wide covalent ligand discovery in native biological systems
Small molecules are powerful tools for investigating protein function, and can serve as leads for new therapeutics, but most human proteins lack known small-molecule ligands; here, a quantitative analysis of cysteine-reactive small-molecule fragments screened against thousands of proteins is reported.
- Keriann M. Backus
- , Bruno E. Correia
- & Benjamin F. Cravatt
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Outlook |
Chemical probes: A shared toolbox
In a pioneering move, the compound JQ1 was released to the community for free. The impact that this has had on research and development is slowly coming into focus.
- Andrew R. Scott
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Letter |
Structure- and function-based design of Plasmodium-selective proteasome inhibitors
Structural and functional characterizations show that the specificity of the Plasmodium falciparum proteasome is sufficiently unique from that of the human proteasome to allow selective targeting with inhibitors.
- Hao Li
- , Anthony J. O’Donoghue
- & Matthew Bogyo
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News |
Dying for a long life
A chemical that stains Alzheimer's-associated proteins may help cells to cope with toxic trash.
- Ewen Callaway
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News |
Alzheimer's-disease probe nears approval
Imaging technique could help to resolve questions about brain plaques associated with the condition.
- Heidi Ledford
Oxidative cyclization reagents reveal tryptophan cation–π interactions