Unusual zwitterionic catalytic site of SARS-CoV-2 main protease revealed by neutron crystallography.

ABSTRACT: The main protease (3CL M^pro) from SARS-CoV-2, the etiological agent of COVID-19, is an essential enzyme for viral replication. 3CL M^pro possesses an unusual catalytic dyad composed of Cys¹⁴⁵ and His⁴¹ residues. A critical question in the field has been what the protonation states of the ionizable residues in the substrate-binding active-site cavity are; resolving this point would help understand the catalytic details of the enzyme and inform rational drug development against this pernicious virus. Here, we present the room-temperature neutron structure of 3CL M^pro, which allowed direct determination of hydrogen atom positions and, hence, protonation states in the protease. We observe that the catalytic site natively adopts a zwitterion

SUBMITTER: Kneller DW 

PROVIDER: S-EPMC7832724 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature