proteases
Research Article | Therapeutics and PreventionA Targeted Computational Screen of the SWEETLEAD Database Reveals FDA-Approved Compounds with Anti-Dengue Viral ActivityNo antiviral therapeutics are currently available for dengue virus infections. By computationally overlaying the three-dimensional (3D) chemical structures of compounds known to inhibit dengue virus over those of compounds known to be safe in humans, we identified three FDA-approved compounds that are attractive candidates for repurposing as antivirals. We identified targets for two previously identified antiviral compounds and revealed...
Research Article | Therapeutics and PreventionIn Vivo Emergence of a Novel Protease Inhibitor Resistance Signature in HIV-1 MatrixProtease inhibitors (PIs) are the second- and last-line therapy for the majority of HIV-infected patients worldwide. Only around 20% of individuals who fail PI regimens develop major resistance mutations in protease. We sought to explore the role of mutations in gag-pro genotypic and phenotypic changes in viruses from six Nigerian patients who failed PI-based regimens without known drug resistance-associated protease...
Research Article | Molecular Biology and PhysiologyFeedback Control of a Two-Component Signaling System by an Fe-S-Binding Receiver DomainTwo-component signal transduction systems (TCSs) are broadly conserved in the bacterial kingdom and generally contain two molecular components, a sensor histidine kinase and a receiver protein. Sensor histidine kinases alter their phosphorylation state in direct response to a physical or chemical cue, whereas receiver proteins “receive” the phosphoryl group from the kinase to regulate a change in cell physiology. We have discovered that...
Research Article | Molecular Biology and PhysiologyA Conserved Regulatory Circuit Controls Large Adhesins in Vibrio choleraeVibrio cholerae, the causative agent of the diarrheal disease cholera, benefits from a sessile biofilm lifestyle that enhances survival outside the host but also contributes to host colonization and infectivity. The bacterial second messenger c-di-GMP has been identified as a central regulator of biofilm formation, including in...
Research Article | Molecular Biology and PhysiologyStructural Basis for the Differential Regulatory Roles of the PDZ Domain in C-Terminal Processing ProteasesPrc, also known previously as Tsp, is the founding member of the carboxyl-terminal processing protease (CTP) family of PDZ domain-containing proteases that include CtpA and CtpB. The substrate-binding PDZ domain is responsible for regulating the protease activity of CTP proteases; however, the regulatory role of PDZ domain is stimulatory in Prc but inhibitory in CtpA/B. By determining a series of crystal structures of Prc in the...
Editor's Pick Research Article | Host-Microbe BiologyStable Occupancy of the Crimean-Congo Hemorrhagic Fever Virus-Encoded Deubiquitinase Blocks Viral InfectionCrimean-Congo hemorrhagic fever virus is an important human pathogen with a wide global distribution for which no therapeutic interventions are available. CCHFV encodes a cysteine protease belonging to the ovarian tumor (OTU) family which is involved in host immune suppression. Here we demonstrate that artificially prolonged binding of the OTU to a substrate inhibits virus infection. This provides novel insights into CCHFV OTU function...
Observation | Molecular Biology and PhysiologyInterplay between the Hsp90 Chaperone and the HslVU Protease To Regulate the Level of an Essential Protein in Shewanella oneidensisMaintaining a healthy proteome is essential in every living cell from bacteria to humans. For example, proteostasis (protein homeostasis) imbalance in humans leads to devastating diseases, including neurodegenerative diseases and cancers. Therefore, proteins need to be assisted from their synthesis to their native folding and ultimately to their degradation. To ensure efficient protein turnover, cells possess an intricate network of...
Research Article | Host-Microbe BiologyProtease-Mediated Growth of Staphylococcus aureus on Host Proteins Is opp3 DependentStaphylococcus aureus has the ability to cause infections in a variety of niches, suggesting a robust metabolic capacity facilitating proliferation under various nutrient conditions. The mature skin abscess is glucose depleted, indicating that peptides and free amino acids are important sources of nutrients for...