NMR Observation of Sulfhydryl Signals in SARS-CoV-2 Main Protease Aids Structural Studies.

ABSTRACT: The 68-kDa homodimeric 3C-like protease of SARS-CoV-2, M^pro (3CL^pro /Nsp5), is a key antiviral drug target. NMR spectroscopy of this large system proved challenging and resonance assignments have remained incomplete. Here we present the near-complete (>97 %) backbone assignments of a C145A variant of M^pro (M^pro _C145A ) both with, and without, the N-terminal auto-cleavage substrate sequence, in its native homodimeric state. We also present SILLY (Selective Inversion of thioL and Ligand for NOESY), a simple yet effective pseudo-3D NMR experiment that utilizes NOEs to identify interactions between Cys-thiol or aliphatic protons, and their spatially proximate backbone amides in a perdeuterated protein background. High protection against hy

SUBMITTER: Robertson AJ 

PROVIDER: S-EPMC9537880 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature