3AVZ

Structure of SARS 3CL protease with peptidic aldehyde inhibitor containing cyclohexyl side chain

3AVZ の概要

• エントリーDOI: 10.2210/pdb3avz/pdb
• 関連するPDBエントリー: 3ATW 3AW0 3AW1
• 関連するBIRD辞書のPRD_ID: PRD_000990
• 分子名称: 3C-Like Proteinase, peptide ACE-SER-ALA-VAL-ALC-HIS-H (3 entities in total)
• 機能のキーワード: hydrolase proteinase converting, designed inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: SARS coronavirus (SARS-CoV); 詳細
• 細胞内の位置: Non-structural protein 3: Host membrane ; Multi-pass membrane protein . Non-structural protein 4: Host membrane ; Multi-pass membrane protein . Non-structural protein 6: Host membrane ; Multi-pass membrane protein . Non-structural protein 7: Host cytoplasm, host perinuclear region . Non-structural protein 8: Host cytoplasm, host perinuclear region . Non-structural protein 9: Host cytoplasm, host perinuclear region . Non-structural protein 10: Host cytoplasm, host perinuclear region : P0C6U8
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34409.31

構造登録者

Akaji, K.,Konno, H.,Mitsui, H.,Teruya, K.,Hattori, Y.,Ozaki, T.,Kusunoki, M.,Sanjho, A. (登録日: 2011-03-09, 公開日: 2011-12-14, 最終更新日: 2023-11-15)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.46 Å)