2A5A

Crystal structure of unbound SARS coronavirus main peptidase in the space group C2

Summary for 2A5A

• Entry DOI: 10.2210/pdb2a5a/pdb
• Related: 2A5I 2A5K
• Descriptor: 3C-like peptidase, CHLORIDE ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: cysteine peptidase, 3c-like, n-finger, chymotrypsin-like fold, long loop, alpha-helical domain, dimer, catalytic dyad, specificity pockets, hydrolase
• Biological source: SARS coronavirus
• Total number of polymer chains: 1
• Total formula weight: 34009.61

Authors

Lee, T.-W.,Cherney, M.M.,Huitema, C.,Liu, J.,James, K.E.,Powers, J.C.,Eltis, L.D.,James, M.N. (deposition date: 2005-06-30, release date: 2005-10-25, Last modification date: 2023-08-23)

Primary citation

Lee, T.-W.,Cherney, M.M.,Huitema, C.,Liu, J.,James, K.E.,Powers, J.C.,Eltis, L.D.,James, M.N.
Crystal Structures of the Main Peptidase from the SARS Coronavirus Inhibited by a Substrate-like Aza-peptide Epoxide
J.Mol.Biol., 353:1137-1151, 2005

PubMed Abstract: The main peptidase (M(pro)) from the coronavirus (CoV) causing severe acute respiratory syndrome (SARS) is one of the most attractive molecular targets for the development of anti-SARS agents. We report the irreversible inhibition of SARS-CoV M(pro) by an aza-peptide epoxide (APE; k(inact)/K(i) = 1900(+/-400) M(-1) s(-1)). The crystal structures of the M(pro):APE complex in the space groups C2 and P2(1)2(1)2(1) revealed the formation of a covalent bond between the catalytic Cys145 S(gamma) atom of the peptidase and the epoxide C3 atom of the inhibitor, substantiating the mode of action of this class of cysteine-peptidase inhibitors. The aza-peptide component of APE binds in the substrate-binding regions of M(pro) in a substrate-like manner, with excellent structural and chemical complementarity. In addition, the crystal structure of unbound M(pro) in the space group C2 revealed that the "N-fingers" (N-terminal residues 1 to 7) of both protomers of M(pro) are well defined and the substrate-binding regions of both protomers are in the catalytically competent conformation at the crystallization pH of 6.5, contrary to the previously determined crystal structures of unbound M(pro) in the space group P2(1).

PubMed: 16219322
DOI: 10.1016/j.jmb.2005.09.004

Experimental method

X-RAY DIFFRACTION (2.08 Å)