Journal Article

USP25 and USP28 are critical deubiquitylases (DUBs) that have been implicated in various diseases, particularly cancer and cardiac dysfunction. Several small-molecule inhibitors have been reported, exhibiting dual inhibitory activity in the low micromolar range. [...]

TBC (Tre2/Bub2/Cdc16) domain-containing proteins constitute the widespread family of GTPase-activating proteins (GAPs). They interact with the Rab superfamily of small GTPases, stimulate GTP hydrolysis, and regulate vesicle trafficking. [...]

The evolution of C4 photosynthesis required extensive modification of ancestral enzymes enabling the development of anefficient carbon concentrating mechanism. A key example is NADP-malic enzyme (NADP-ME), which, in maize and sorghum—members of the same C4 lineage—underwent gene duplication and neofunctionalization, resulting in 2 plastidic isoformswith distinct oligomeric states: a tetrameric C4-specific isoform and a dimeric housekeeping (nonC4) isoform. [...]

Aspartate transcarbamoylase (ATC) catalyzes the committed and rate-limiting step in the pyrimidine de novo biosynthesis pathway. While previously suggested to be a potential target for antimalarial, antitubercular, and antioncologic drug discovery, we hypothesized that an existing compound library of ATC inhibitors designed from one scaffold by fragment screening against Plamodium falciparum ATC (PfATC) may also contain inhibitors of Trypanosoma cruzi ATC (TcATC). [...]

Herein, we present crystal structures of proteins adopting a fold not identified among known -solenoids in current structural databases, a Knotted Solenoid. These proteins exhibit a characteristic solenoidal architecture, closely resembling -solenoid proteins. [...]

Mono(2-hydroxyethyl) terephthalate (MHET) esterases (MHETases) are enzymes implicated in polyethylene terephthalate (PET) biodegradation. The present study elucidates the structural determinants that result in increased MHET degradation by a feruloyl esterase, which has been engineered to resemble the MHETase active site. [...]

N6-methyladenosine (m6A) is the most prevalent internal modification in eukaryotic messenger RNA. Dysregulation of m6A-RNA signaling has been implicated in a wide range of human diseases. [...]

Second messenger signaling through cyclic dinucleotides regulates critical processes in pathogenic bacteria. DhhP is a phosphodiesterase that regulates levels of cyclic di-AMP (c-di-AMP), an essential second messenger, in Borrelia. [...]

Antimicrobial resistance is one of the most significant global health threats of the 21st century, demanding urgent strategies for the development of novel therapeutic approaches. Urease, a nickel-dependent enzyme absent in the human proteome, represents an attractive target for drug development because several urease-expressing bacterial pathogens play a critical role in pathogenesis. [...]

Nonstructural protein 3 (nsp3) is crucial for SARS-CoV-2 infection. It is the largest protein of the virus with roughly 2000 residues, and a major drug target. [...]