Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug.

We report two structures of the human voltage-gated potassium channel (Kv) Kv1.3 in immune cells alone (apo-Kv1.3) and bound to an immunomodulatory drug called dalazatide (dalazatide-Kv1.

Modulation of Lymphocyte Potassium Channel K1.3 by Membrane-Penetrating, Joint-Targeting Immunomodulatory Plant Defensin.

We describe a cysteine-rich, membrane-penetrating, joint-targeting, and remarkably stable peptide, EgK5, that modulates voltage-gated K1.3 potassium channels in T lymphocytes by a distinctive mechanism. EgK5 enters plasma membranes and binds to K1.

Contributions of natural products to ion channel pharmacology.

Covering: Up to 2020Ion channels are a vast super-family of membrane proteins that play critical physiological roles in excitable and non-excitable cells. Their biomedical importance makes them valuable and attractive drug targets for neurological, cardiovascular, gastrointestinal and metabolic diseases, and for cancer therapy and immune modulation. Current therapeutics target only a minor subset of ion channels, leaving a large unexploited space within the ion channel field.

Venom-Derived Peptide Modulators of Cation-Selective Channels: Friend, Foe or Frenemy.

Ion channels play a key role in our body to regulate homeostasis and conduct electrical signals. With the help of advances in structural biology, as well as the discovery of numerous channel modulators derived from animal toxins, we are moving toward a better understanding of the function and mode of action of ion channels. Their ubiquitous tissue distribution and the physiological relevancies of their opening and closing suggest that cation channels are particularly attractive drug targets, and years of research has revealed a variety of natural toxins that bind to these channels and alter their function.

In vitro assembly of polymorphic virus-like particles from the capsid protein of a nodavirus.

Viral capsid proteins are programmed to assemble into homogeneous structures in native environments; but the molecular details of these assembly pathways are seldom clearly understood. In order to define the chain of events in the construction of a minimal system, we attempted controlled assembly of the capsid protein of a small insect nodavirus, Flock House Virus (FHV). Bacterial expression of the FHV capsid protein, and subsequent in vitro assembly, generated a heterogeneous population of closed particles.

Engineering Virus Capsids Into Biomedical Delivery Vehicles: Structural Engineering Problems in Nanoscale.

Virus capsids have evolved to protect the genome sequestered in their interior from harsh environmental conditions, and to deliver it safely and precisely to the host cell of choice. This characteristic makes them naturally perfect containers for delivering therapeutic molecules to specific locations. Development of an ideal virus-based nano-container for medical usage requires that the capsid be converted into a targetable protein cage which retains the original stability, flexibility and host cell penetrating properties of the native particles, without the associated immunogenicity, and is able to encapsulate large quantities of therapeutic or diagnostic material.

Evaluation of salivary and serum lipid peroxidation, and glutathione in oral leukoplakia and oral squamous cell carcinoma.

Lipid peroxidation induced by reactive oxygen species (ROS) is involved in the pathogenesis of malignancy. Overall, lipid peroxidation levels are indicated by malondialdehyde (MDA), which is the most frequently used biomarker to detect oxidative changes. Antioxidant defense systems such as glutathione (GSH) limit cell injury induced by ROS.