2QCY

Crystal Structure of a monomeric form of Severe Acute Respiratory Syndrome (SARS) 3C-like protease mutant

Summary for 2QCY

• Entry DOI: 10.2210/pdb2qcy/pdb
• Related: 2QC2
• Descriptor: 3C-like proteinase (2 entities in total)
• Functional Keywords: hydrolase, cysteine peptidase, 3c-like, n-finger, chymotrypsin-like fold, catalytic dyad, c-terminal domain
• Biological source: SARS coronavirus
• Total number of polymer chains: 1
• Total formula weight: 33790.52

Authors

Shi, J.H.,Sivaraman, J.,Song, J.X. (deposition date: 2007-06-20, release date: 2008-03-11, Last modification date: 2024-02-21)

Primary citation

Shi, J.,Sivaraman, J.,Song, J.
Mechanism for controlling the dimer-monomer switch and coupling dimerization to catalysis of the severe acute respiratory syndrome coronavirus 3C-like protease.
J.Virol., 82:4620-4629, 2008

PubMed Abstract: Unlike 3C protease, the severe acute respiratory syndrome coronavirus (SARS-CoV) 3C-like protease (3CLpro) is only enzymatically active as a homodimer and its catalysis is under extensive regulation by the unique extra domain. Despite intense studies, two puzzles still remain: (i) how the dimer-monomer switch is controlled and (ii) why dimerization is absolutely required for catalysis. Here we report the monomeric crystal structure of the SARS-CoV 3CLpro mutant R298A at a resolution of 1.75 A. Detailed analysis reveals that Arg298 serves as a key component for maintaining dimerization, and consequently, its mutation will trigger a cooperative switch from a dimer to a monomer. The monomeric enzyme is irreversibly inactivated because its catalytic machinery is frozen in the collapsed state, characteristic of the formation of a short 3(10)-helix from an active-site loop. Remarkably, dimerization appears to be coupled to catalysis in 3CLpro through the use of overlapped residues for two networks, one for dimerization and another for the catalysis.

PubMed: 18305031
DOI: 10.1128/JVI.02680-07

Experimental method

X-RAY DIFFRACTION (1.75 Å)