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

Summary for 4MDS

• Entry DOI: 10.2210/pdb4mds/pdb
• Descriptor: 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)
• Functional Keywords: chymotrypsin-like, protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 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: 1
• Total formula weight: 34144.06

Authors

Mesecar, A.D.,Grum-Tokars, V. (deposition date: 2013-08-23, release date: 2013-10-02, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.598 Å)