3aw0 | pdb_00003aw0

Structure of SARS 3CL protease with peptidic aldehyde inhibitor

spinqualitylabelsall models 3aw0, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3aw0 is a 2 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: ACE, HSO Related: 3atw, 3avz, 3aw1 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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