The insulin receptor is a membrane protein responsible for regulation of
nutrient balance and therefore an attractive target in the treatment of
diabetes and metabolic syndrome. Pharmacology of the insulin receptor
involves two distinct mechanisms, (1) activation of the receptor by
insulin mimetics that bind in the extracellular domain and (2)
inhibition of the receptor tyrosine kinase enzymatic activity in the
cytoplasmic domain. While a complete structural picture of the
full-length receptor comprising the entire sequence covering
extracellular, transmembrane, juxtamembrane and cytoplasmic domains is
still elusive, recent progress through cryoelectron microscopy has made
it possible to describe the initial insulin ligand binding events at
atomistic detail. We utilize this opportunity to obtain structural
insights into the pharmacology of the insulin receptor. To this end, we
conducted a comprehensive docking study of known ligands to the new
structures of the receptor. Through this approach, we provide an
in-depth, structure-based review of human insulin receptor pharmacology
in light of the new structures.
Structure‐based survey of ligand binding in the human insulin receptor
