Modification of Glycan binding Specificity of E-selectin from sLex to 6′-sulfo-sLex with double mutations E92A/E107A

A group from Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, etc. has reported that the specificity of E-selectin could be modified from sLex to 6′-sulfo-sialyl Lewis X with introducing double mutations.

Although lectins are often used to detect glycans, their application to sulfated glycans is challenging due to the paucity of sulfate-recognizing lectins as well as their broad or mixed specificities.

In this work, the binding specificity of E-selectin was modified by removing destabilizing steric and electrostatic interactions between the 6′-sulfate and E92 and E107 with E92A/E107A mutations, to show binding specificity to 6′-sulfo-sialyl Lewis X (6′-sulfo-sLex). As is known, E-selectin shows specific binding to non-sulfated ligand, sLex.
This new specificity mimics that of the unrelated protein Siglec-8, for which 6′-sulfo-sLex is its preferred ligand.