Anan GS
SARS-CoV-2 S protein:ACE2 interaction reveals novel allosteric targets
The spike (S) protein is the main handle for SARS-CoV-2 to enter host cells via surface angiotensin-converting enzyme 2 (ACE2) receptors. How ACE2 binding activates proteolysis of S protein is unknown.
ReadSynergistic Allostery in Multiligand-Protein Interactions
Rational drug design has traditionally targeted orthosteric sites for common biological ligands such as nucleotides. Loss of specificity is a major disadvantage in such an approach. Allosteric site(s) offer an alternative, and a combination of orthosteric targeting and allosteric drugs offer greater potency and specificity. However, in vitro quantitation of the combinatorial effects of two or more drugs targeting a common protein has remained a challenge. We present a simple method to quantify combinatorial effects in a dual-liganded kinase model by hydrogen-deuterium exchange mass spectrometry. This method is easily scalable for proteins with more than two ligands, as well as for rapid pairwise screening of candidate molecules.
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