4MDS

Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: identification of ML300 and non-covalent nanomolar inhibitors with an induced-fit binding

4MDS の概要

• エントリーDOI: 10.2210/pdb4mds/pdb
• 分子名称: 3C-like proteinase, N-[4-(acetylamino)phenyl]-2-(1H-benzotriazol-1-yl)-N-[(1R)-2-[(2-methylbutan-2-yl)amino]-1-(1-methyl-1H-pyrrol-2-yl)-2-oxoethyl]acetamide, DIMETHYL SULFOXIDE, ... (4 entities in total)
• 機能のキーワード: chymotrypsin-like, protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: SARS coronavirus (SARS-CoV)
• 細胞内の位置: 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
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34144.06

構造登録者

Mesecar, A.D.,Grum-Tokars, V. (登録日: 2013-08-23, 公開日: 2013-10-02, 最終更新日: 2024-02-28)

主引用文献

Turlington, M.,Chun, A.,Tomar, S.,Eggler, A.,Grum-Tokars, V.,Jacobs, J.,Daniels, J.S.,Dawson, E.,Saldanha, A.,Chase, P.,Baez-Santos, Y.M.,Lindsley, C.W.,Hodder, P.,Mesecar, A.D.,Stauffer, S.R.
Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: Identification of ML300 and noncovalent nanomolar inhibitors with an induced-fit binding.
Bioorg.Med.Chem.Lett., 23:6172-6177, 2013

PubMed Abstract: Herein we report the discovery and SAR of a novel series of SARS-CoV 3CLpro inhibitors identified through the NIH Molecular Libraries Probe Production Centers Network (MLPCN). In addition to ML188, ML300 represents the second probe declared for 3CLpro from this collaborative effort. The X-ray structure of SARS-CoV 3CLpro bound with a ML300 analog highlights a unique induced-fit reorganization of the S2-S4 binding pockets leading to the first sub-micromolar noncovalent 3CLpro inhibitors retaining a single amide bond.

PubMed: 24080461
DOI: 10.1016/j.bmcl.2013.08.112

実験手法

X-RAY DIFFRACTION (1.598 Å)