Carbon dioxide (CO2) is a product of cellular respiration that can also serve as a post-translational modification (PTM) through covalent protein modification. A new chemoproteomic strategy enables the capture of functional CO2-dependent carboxylation on lysine residues of proteins.

The rising threat of antifungal resistance means that alternative therapeutics need to be considered. New research explores the biochemical basis of virulence inhibition by mucus glycans against the fungal pathogen Candida albicans.

A fungal ten-eleven translocation (TET) dioxygenase homolog, CcTet, is found to have both 5-methylcytosine (5mC) and N6-methyladenine (6mA) demethylase activity. Structure-based engineering of CcTet yielded a 6mA-specific demethylase, offering a useful tool for the manipulation and functional study of 6mA.

The discovery of long-existing terpenoid biosynthetic pathways in soft corals changes the way specialized metabolism in animals is thought about, and opens unprecedented access to the largely untapped treasure trove of medicinal marine natural products.

Controlling kinase inhibitors’ residence time via reversible covalent binding is of high interest in drug discovery. Tuning reversible covalent binding kinetics using a pan-kinase inhibitor that reacts with the catalytic lysine enabled exquisite temporal selectivity in vitro and in vivo.

Protein arginine methyltransferases (PRMTs) are overexpressed in many cancer types, including triple-negative breast cancer (TNBC). A new study shows that a reversible inhibitor of type I PRMTs suppresses TNBC tumor growth by inducing a viral mimicry response with retained introns.

Chemical methods that integrate analytical and quantitative measurements of metabolites with the ability to alter metabolic processes offer powerful tools for modulating biology and physiology.

Natural enzyme complexes can rapidly change configurations to respond to intracellular cues. Now CRISPR enzymes and programmable RNA scaffolds allow synthetic enzyme complexes to be assembled and disassembled on demand.

Microproteins can be generated by a shift in the reading frame during translation. A chemoproteomics approach led to the identification of MINAS-60 as an alternative microprotein that regulates the assembly of the pre-60S ribosome.

The cryo-electron microscopy structure of a fluoroquinolone efflux transporter, NorA, in complex with an antibody fragment provides a new strategy whereby peptide inhibitors derived from antibody loops could be used to block antibiotic efflux in a drug-resistant superbug.

Chemoproteomics reveals a cysteine oxidation event that inhibits the maturation process of a lysosomal protease, enabling its secretion into the extracellular space during infection-induced tumorigenesis. A recent study offers a new mechanistic paradigm for redox-dependent regulation of protein trafficking.

Precision oncology requires an understanding of the genes and pathways that dictate therapeutic response. Through specialized analysis of drug sensitivity patterns across hundreds of genomically annotated cancer cell lines, specific and actionable drivers of intrinsic resistance have been identified.

Despite well-established tumorigenic roles of KRAS mutants, targeting their smooth surfaces was a challenge, which was overcome through the development of G12C-specific covalent inhibitors. A new study shows that optimizing non-covalent interactions with a cryptic pocket produces remarkable potency for another hotspot mutation.

Natural self-cleaving RNAs employ a wide range of catalytic strategies, but it is not known whether artificial ribozymes are capable of the same catalytic diversity. New structures of a methyltransferase ribozyme reveal the potential variety of RNA reactions and mechanisms.