Crystal structure of SARS 3CL mutant C145A in a product-bound state: implication for the design of structure-based inhibitors

A newly identified severe acute respiratory syndrome coronavirus
(SARS-CoV) is the etiological agent responsible for the outbreak of
severe acute respiratory syndrome (SARS). The 3C-like proteinase (also
called main proteinase) is a key enzyme for mediating viral replication
and transcription through extensive proteolytic processing and an
essential target for drug development. One of the catalytic residues of
SARS 3C-like protease, Cys145, was replaced with Ala and the C145A
mutant was over-expressed, purified and crystallized. The plate-like
crystal diffracts to 2.5Å and belongs to C2 space group. There is one
dimer in an asymmetric unit. The structure revealed that the active site
region is penetrated by another monomer which belongs to another
asymmetric unit. This study provides a basic understanding of the
substrate binding, which is helpful for the design of structure-based
inhibitors SARS and related coronaviruses.