3F9E

Crystal Structure of the S139A mutant of SARS-Coronovirus 3C-like Protease

Summary for 3F9E

• Entry DOI: 10.2210/pdb3f9e/pdb
• Related: 3F9F 3F9G 3F9H
• Descriptor: 3C-like proteinase (2 entities in total)
• Functional Keywords: protease, cytoplasm, hydrolase, membrane, metal-binding, ribosomal frameshifting, rna-binding, thiol protease, transmembrane, zinc, zinc-finger
• 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: 34004.76

Authors

Hu, T.,Li, L.,Jiang, H.,Shen, X. (deposition date: 2008-11-13, release date: 2009-09-29, Last modification date: 2023-12-27)

Primary citation

Hu, T.,Zhang, Y.,Li, L.,Wang, K.,Chen, S.,Chen, J.,Ding, J.,Jiang, H.,Shen, X.
Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like protease cause different conformational changes in crystal structure.
Virology, 388:324-334, 2009

PubMed Abstract: The 3C-like protease of SARS coronavirus (SARS-CoV 3CL(pro)) is vital for SARS-CoV replication and is a promising drug target. It has been extensively proved that only the dimeric enzyme is active. Here we discovered that two adjacent mutations (Ser139_Ala and Phe140_Ala) on the dimer interface resulted in completely different crystal structures of the enzyme, demonstrating the distinct roles of these two residues in maintaining the active conformation of SARS-CoV 3CL(pro). S139A is a monomer that is structurally similar to the two reported monomers G11A and R298A. However, this mutant still retains a small fraction of dimer in solution, which might account for its remaining activity. F140A is a dimer with the most collapsed active pocket discovered so far, well-reflecting the stabilizing role of this residue. Moreover, a plausible dimerization mechanism was also deduced from structural analysis. Our work is expected to provide insight on the dimerization-function relationship of SARS-CoV 3CL(pro).

PubMed: 19409595
DOI: 10.1016/j.virol.2009.03.034

Experimental method

X-RAY DIFFRACTION (2.5 Å)