Unusual zwitterionic catalytic site of SARS–CoV-2 main protease revealed by neutron crystallography
Daniel W. Kneller, G.N. Phillips, Kevin L. Weiss, Swati Pant, Qiu Zhang, Hugh O’Neill, Leighton Coates, Andrey Kovalevsky
Abstract
is doubly protonated and positively charged, instead of the neutral unreactive state usually envisaged. The neutron structure also identified the protonation states, and thus electrical charges, of all other amino acid residues and revealed intricate hydrogen-bonding networks in the active-site cavity and at the dimer interface. The fine atomic details present in this structure were made possible by the unique scattering properties of the neutron, which is an ideal probe for locating hydrogen positions and experimentally determining protonation states at near-physiological temperature. Our observations provide critical information for structure-assisted and computational drug design, allowing precise tailoring of inhibitors to the enzyme's electrostatic environment.