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Bioymifi, a small-molecule death receptor 5 (DR5) agonist, induces selective cancer cell apoptosis as a single agent or in synergy with small-molecule Smac mimetics.
Cholic acid and 24(S),25-epoxycholesterol are endogenous midbrain LXR ligands that are neurogenic for red nucleus or dopaminergic neurons, respectively.
N6-Threonylcarbamoyladenosine (t6A), a modified nucleotide found in certain tRNAs, has an essential role in translational fidelity. New analytical data reveal that t6A adopts a cyclic form (ct6A) in cells and has led to the identification of the enzymes that convert t6A to ct6A.
Quantification of cytosolic glutathione redox potential leads to the discovery that the ABC-C transporter Ycf1 rapidly transports oxidized glutathione (GSSG) into vacuoles and whole-cell GSSG should not be used as a proxy for cytosolic GSSG.
Aerobic inactivation of hydrogenases is a serious limitation to applications of the enzyme in biotechnology and has been extensively studied. A recent investigation combining electrochemical and spectroscopic methods shows that the molecular species that form as a result of exposure to O2 can be formed anaerobically and thus cannot involve incorporation of oxygen in the enzyme.
Conformational targeting enabled the creation of a ubiquitin variant that specifically inhibits the deubiquitinating enzyme ubiquitin-specific protease 7 (also known as HAUSP). Generation of such tools is essential to unravel the complexities of ubiquitin signaling, but how general is this approach?
Public-private partnerships can reinvigorate precompetitive scientific research and de-risk drug discovery programs to help them meet demand for better and safer therapies.
New, bioactive marine sponge compounds that function as inhibitors of the poly (ADP-ribose) polymerase family of proteins have now been identified to promote the correction of cystic fibrosis. Poly (ADP-ribose) polymerase inhibitors may be managers of proteostasis biology, consistent with their role (or roles) in remediation of inflammatory states.
Chemical probes are urgently needed to functionally annotate hitherto-untargeted kinases and stimulate new drug discovery efforts to address unmet medical needs. The size of the human kinome combined with the high cost associated with probe generation severely limits access to new probes. We propose a large-scale public-private partnership as a new approach that offers economies of scale, minimized redundancy and sharing of risk and cost.
An allosteric activator of Hsp70 mimics Hip and reduces neurotoxicity in a model for spinobulbar muscular atrophy by promoting ubiquitination and degradation of oligomeric polyglutamine-containing clients.
Structural characterization of an artificial zinc-dependent enzyme created by in vitro evolution yields a new, flexible fold that challenges straightforward definitions of active site residues and raises questions about protein evolution.
Allosteric conformations and proteolytic activities of each subunit of the trimeric E. coli DegS protease share a cooperatively coupled energy landscape that allows regulation via the binding of substrate and OMP peptides.
