3AW1

Structure of SARS 3CL protease auto-proteolysis resistant mutant in the absent of inhibitor

Summary for 3AW1

• Entry DOI: 10.2210/pdb3aw1/pdb
• Related: 3AVZ 3AW0
• Descriptor: 3C-Like Proteinase (2 entities in total)
• Functional Keywords: hydrolase proteinase converting, hydrolase
• Biological source: SARS coronavirus (SARS-CoV)
• Cellular location: Non-structural protein 3: Host membrane; Multi-pass membrane protein (Potential). Non-structural protein 4: Host membrane; Multi-pass membrane protein (Potential). Non-structural protein 6: Host membrane; Multi-pass membrane protein (Potential). Non-structural protein 7: Host cytoplasm, host perinuclear region (By similarity). Non-structural protein 8: Host cytoplasm, host perinuclear region (By similarity). Non-structural protein 9: Host cytoplasm, host perinuclear region (By similarity). Non-structural protein 10: Host cytoplasm, host perinuclear region (By similarity): P0C6U8
• Total number of polymer chains: 2
• Total formula weight: 67665.20

Authors

Akaji, K.,Konno, H.,Mitsui, H.,Teruya, K.,Hattori, Y.,Ozaki, T.,Kusunoki, M.,Sanjho, A. (deposition date: 2011-03-09, release date: 2011-12-14, Last modification date: 2023-11-01)

Primary citation

Akaji, K.,Konno, H.,Mitsui, H.,Teruya, K.,Shimamoto, Y.,Hattori, Y.,Ozaki, T.,Kusunoki, M.,Sanjoh, A.
Structure-Based Design, Synthesis, and Evaluation of Peptide-Mimetic SARS 3CL Protease Inhibitors.
J.Med.Chem., 54:7962-7973, 2011

PubMed Abstract: The design and evaluation of low molecular weight peptide-based severe acute respiratory syndrome (SARS) chymotrypsin-like protease (3CL) protease inhibitors are described. A substrate-based peptide aldehyde was selected as a starting compound, and optimum side-chain structures were determined, based on a comparison of inhibitory activities with Michael type inhibitors. For the efficient screening of peptide aldehydes containing a specific C-terminal residue, a new approach employing thioacetal to aldehyde conversion mediated by N-bromosuccinimide was devised. Structural optimization was carried out based on X-ray crystallographic analyses of the R188I SARS 3CL protease in a complex with each inhibitor to provide a tetrapeptide aldehyde with an IC(50) value of 98 nM. The resulting compound carried no substrate sequence, except for a P(3) site directed toward the outside of the protease. X-ray crystallography provided insights into the protein-ligand interactions.

PubMed: 22014094
DOI: 10.1021/jm200870n

Experimental method

X-RAY DIFFRACTION (2 Å)