2GT7

Crystal structure of SARS coronavirus main peptidase at pH 6.0 in the space group P21

Summary for 2GT7

• Entry DOI: 10.2210/pdb2gt7/pdb
• Related: 2GT8 2GTB
• Descriptor: 3C-like proteinase, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID (3 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
• 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). Helicase: Host endoplasmic reticulum-Golgi intermediate compartment (Potential). Uridylate-specific endoribonuclease: Host cytoplasm, host perinuclear region (By similarity): P59641
• Total number of polymer chains: 2
• Total formula weight: 67948.51

Authors

Lee, T.-W.,Cherney, M.M.,Huitema, C.,Liu, J.,James, K.E.,Powers, J.C.,Eltis, L.D.,James, M.N.G. (deposition date: 2006-04-27, release date: 2006-12-26, Last modification date: 2024-02-14)

Primary citation

Lee, T.W.,Cherney, M.M.,Liu, J.,James, K.E.,Powers, J.C.,Eltis, L.D.,James, M.N.G.
Crystal Structures Reveal an Induced-fit Binding of a Substrate-like Aza-peptide Epoxide to SARS Coronavirus Main Peptidase.
J.Mol.Biol., 366:916-932, 2007

PubMed Abstract: The SARS coronavirus main peptidase (SARS-CoV M(pro)) plays an essential role in the life-cycle of the virus and is a primary target for the development of anti-SARS agents. Here, we report the crystal structure of M(pro) at a resolution of 1.82 Angstroms, in space group P2(1) at pH 6.0. In contrast to the previously reported structure of M(pro) in the same space group at the same pH, the active sites and the S1 specificity pockets of both protomers in the structure of M(pro) reported here are in the catalytically competent conformation, suggesting their conformational flexibility. We report two crystal structures of M(pro) having an additional Ala at the N terminus of each protomer (M(+A(-1))(pro)), both at a resolution of 2.00 Angstroms, in space group P4(3)2(1)2: one unbound and one bound by a substrate-like aza-peptide epoxide (APE). In the unbound form, the active sites and the S1 specificity pockets of both protomers of M(+A(-1))(pro) are observed in a collapsed (catalytically incompetent) conformation; whereas they are in an open (catalytically competent) conformation in the APE-bound form. The observed conformational flexibility of the active sites and the S1 specificity pockets suggests that these parts of M(pro) exist in dynamic equilibrium. The structural data further suggest that the binding of APE to M(pro) follows an induced-fit model. The substrate likely also binds in an induced-fit manner in a process that may help drive the catalytic cycle.

PubMed: 17196984
DOI: 10.1016/j.jmb.2006.11.078

Experimental method

X-RAY DIFFRACTION (1.82 Å)