| Structural highlights
3atw is a 4 chain structure with sequence from Sars coronavirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | NonStd Res: | , , |
| Gene: | 1a (SARS coronavirus) |
| Activity: | SARS coronavirus main proteinase, with EC number 3.4.22.69 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Publication Abstract from PubMed
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.
Structure-Based Design, Synthesis, and Evaluation of Peptide-Mimetic SARS 3CL Protease Inhibitors.,Akaji K, Konno H, Mitsui H, Teruya K, Shimamoto Y, Hattori Y, Ozaki T, Kusunoki M, Sanjoh A J Med Chem. 2011 Dec 8;54(23):7962-73. Epub 2011 Nov 9. PMID:22014094[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. 2011 Dec 8;54(23):7962-73. Epub 2011 Nov 9. PMID:22014094 doi:10.1021/jm200870n
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