2GX4

Crystal structure of SARS coronavirus 3CL protease inhibitor complex

Summary for 2GX4

• Entry DOI: 10.2210/pdb2gx4/pdb
• Related: 1Z1I 1Z1J
• Descriptor: 3C-like proteinase, N-[(BENZYLOXY)CARBONYL]-O-(TERT-BUTYL)-L-THREONYL-3-CYCLOHEXYL-N-[(1S)-2-HYDROXY-1-{[(3S)-2-OXOPYRROLIDIN-3-YL]METHYL}ETHYL]-L-ALANINAMIDE (3 entities in total)
• Functional Keywords: sars, 3cl protease, inhibitor complex, hydrolase
• Biological source: SARS coronavirus
• Total number of polymer chains: 1
• Total formula weight: 34479.40

Authors

Hsu, M.F.,Wang, A.H.-J. (deposition date: 2006-05-08, release date: 2007-05-08, Last modification date: 2024-10-23)

Primary citation

Yang, S.,Chen, S.J.,Hsu, M.F.,Wu, J.D.,Tseng, C.T.,Liu, Y.F.,Chen, H.C.,Kuo, C.W.,Wu, C.S.,Chang, L.W.,Chen, W.C.,Liao, S.Y.,Chang, T.Y.,Hung, H.H.,Shr, H.L.,Liu, C.Y.,Huang, Y.A.,Chang, L.Y.,Hsu, J.C.,Peters, C.J.,Wang, A.H.,Hsu, M.C.
Synthesis, crystal structure, structure-activity relationships, and antiviral activity of a potent SARS coronavirus 3CL protease inhibitor.
J.Med.Chem., 49:4971-4980, 2006

PubMed Abstract: A potent SARS coronavirus (CoV) 3CL protease inhibitor (TG-0205221, Ki = 53 nM) has been developed. TG-0205221 showed remarkable activity against SARS CoV and human coronavirus (HCoV) 229E replications by reducing the viral titer by 4.7 log (at 5 microM) for SARS CoV and 5.2 log (at 1.25 microM) for HCoV 229E. The crystal structure of TG-0205221 (resolution = 1.93 A) has revealed a unique binding mode comprising a covalent bond, hydrogen bonds, and numerous hydrophobic interactions. Structural comparisons between TG-0205221 and a natural peptide substrate were also discussed. This information may be applied toward the design of other 3CL protease inhibitors.

PubMed: 16884309
DOI: 10.1021/jm0603926

Experimental method

X-RAY DIFFRACTION (1.93 Å)