Volume 18 Issue 7, July 2022

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.

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.

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 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.

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.

Several venomous predators and pathogens use insulins to capture prey and to manipulate host physiology. This Review provides an overview of the discovery and potential biomedical application of these and other weaponized hormones found in nature.

Chemical proteomics analysis of human gastric cells revealed that infection with the stomach bacterium Helicobacter pylori decreases reactivity of legumain Cys219, which alters legumain processing and promotes xenograft tumor growth.

Cryo-EM analysis of the quinolone transporter NorA in complex with synthetic antigen-binding fragments (Fabs) inspired peptide mimics of the Fabs that inhibit methicillin-resistant Staphylococcus aureus in combination with the antibiotic norfloxacin.

Using magnetic tweezers, Choi et al. revealed the asymmetric folding pathway of GLUT3, a human glucose transporter, suggesting the active effect of cells in helping glucose transporters overcome folding challenges when forming channels for sugar molecules.

Biochemical and structural characterization of the bifunctional lanthipeptide protease EryP enables identification of a regulatory interdomain calcium-binding site and leads to a strategy to engineer related enzymes for enhanced catalytic activity.

A fungal dioxygenase CcTet displays robust demethylation activity against both N⁶-methyladenosine (6mA) and 5-methylcytosine on duplex DNA, while its D337F mutant exhibits specific activity against 6mA, providing a useful tool for 6mA functional study.

A DNA recording method based on an enhanced dCas12a base editor system enables the parallel and scalable recording of cellular signaling events in multiple mammalian cell types.

LRP8 regulation of cellular selenium promotes ferroptosis resistance in cancer. Low selenium leads to ribosome stalling, ribosome collisions and early GPX4 translation termination.

Glycomic profiling of mucosal surfaces identified O-mucin glycoconjugate motifs that regulate Candida albicans virulence. Synthetic analogs based on these glycans suppress fungal filamentation, offering potential for antifungal development.

Sea stars and sea cucumbers biosynthesize protective glycosylated steroids and triterpenes via divergent oxidosqualene cyclases (OSCs) that produce these distinct saponins in different species as well as in different tissues of a single species.

Using isocyanic acid as a CO₂ analog generates a stable mimic of lysine carboxylation, enabling development of a quantitative chemoproteomic approach to identify this modification in proteins and explore the lysine carboxylome of a cyanobacterium.