Structural Evidence For An Induced Fit Of E-selectin Upon Small Molecule Ligand Binding

摘要

Dysfunction of the C-type lectin E-selectin can lead to various inflammatory diseases, e.g. rheumatoid arthritis, asthma or reperfusion injury. Therefore, glycomimetic antagonists are considered as therapeutic agent for the treatment of E-selectin related diseases. Structural studies on E-selectin were previously performed only in absence of ligand [1] and soaked with the natural ligand sialyl Lewis~x (sLe~x) [2]. The first four domains of hE-selectin were expressed in chemically modified CHO cells yielding endoglycosidase sensitive protein, which was deglycosylated with EndoHf and functionally purified.