Structure-Activity Relationships of Ligand Binding to Oxysterol-Binding Protein (OSBP) and OSBP-Related Protein 4.

Oxysterol-binding protein (OSBP) and OSBP-related protein 4 (ORP4) have emerged as potentially druggable targets in antiviral and precision cancer drug development. Multiple structurally diverse small molecules function through targeting the OSBP/ORP family of proteins, including the antiviral steroidal compounds OSW-1 and T-00127-HEV2. Here, the structure-activity relationships of oxysterols and related compound binding to human OSBP and ORP4 are characterized.

ParD Antitoxin Hotspot Alters a Disorder-to-Order Transition upon Binding to Its Cognate ParE Toxin, Lessening Its Interaction Affinity and Increasing Its Protease Degradation Kinetics.

Type-II toxin-antitoxin (TA) systems are comprised of two tightly interacting proteins, and operons encoding these systems have been identified throughout the genomes of bacteria. In contrast to secretion system effector-immunity pairs, TA systems must remain paired to protect the host cell from toxicity. Continual depletion of the antitoxin results in a shorter half-life than that of the toxin, though it is unclear if antitoxins can be effectively degraded when complexed with toxins.