OpenAccess

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. [...]

We perform the first dedicated comparison of five hadronic codes (AM$^{3}$, ATHEνA, B13, LeHa-Paris, and LeHaMoC) that have been extensively used in modeling the spectral energy distribution (SED) of jetted active galactic nuclei. The purpose of this comparison is to identify the sources of systematic errors (e.g., implementation method of proton–photon interactions) and to quantify the expected dispersion in numerical SED models computed with the five codes. [...]

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. [...]

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. [...]

Both histone acetyltransferases (HATs) and histone deacetylases (HDACs) control the acetylation state of conserved lysine residues in histone tails. Thereby, modulating chromatin structure and gene transcription. [...]

Copper plays essential roles in enzymatic activity, redox reactions, and cellular signalling but becomes toxic when redox homeostasis is disrupted. While Cu(II) reduction is commonly attributed to unfolded or amyloid proteins, here we show that the well-folded plasma protein human serum albumin (HSA) intrinsically reduces Cu(II) to Cu(I) in the absence of external reductants. [...]

The intrinsically disordered MYC proteins are master regulators of cellular growth and function, but when deregulated they become cancer drivers. MYC-protein interactions are key to oncogenesis, and while disrupting such interactions would be of significant therapeutic benefit, the intrinsically disordered properties of MYC have dramatically hampered their characterization. [...]

We investigate non-local conserved charges in perturbed two-dimensional conformal field theories (CFT) from the point of view of the 3d symmetry TFT (SymTFT) of the unperturbed theory. In the SymTFT we state a simple commutation condition which results in a pair of compatible bulk and defect perturbations, such that the perturbed line defects are conserved in the perturbed CFT. [...]