1z1j
From Proteopedia
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'''Crystal structure of SARS 3CLpro C145A mutant''' | '''Crystal structure of SARS 3CLpro C145A mutant''' | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Hsu, M F.]] | [[Category: Hsu, M F.]] | ||
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Revision as of 14:04, 3 May 2008
Crystal structure of SARS 3CLpro C145A mutant
Overview
Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel human coronavirus. Viral maturation requires a main protease (3CL(pro)) to cleave the virus-encoded polyproteins. We report here that the 3CL(pro) containing additional N- and/or C-terminal segments of the polyprotein sequences undergoes autoprocessing and yields the mature protease in vitro. The dimeric three-dimensional structure of the C145A mutant protease shows that the active site of one protomer binds with the C-terminal six amino acids of the protomer from another asymmetric unit, mimicking the product-bound form and suggesting a possible mechanism for maturation. The P1 pocket of the active site binds the Gln side chain specifically, and the P2 and P4 sites are clustered together to accommodate large hydrophobic side chains. The tagged C145A mutant protein served as a substrate for the wild-type protease, and the N terminus was first digested (55-fold faster) at the Gln(-1)-Ser1 site followed by the C-terminal cleavage at the Gln306-Gly307 site. Analytical ultracentrifuge of the quaternary structures of the tagged and mature proteases reveals the remarkably tighter dimer formation for the mature enzyme (K(d) = 0.35 nm) than for the mutant (C145A) containing 10 extra N-terminal (K(d) = 17.2 nM) or C-terminal amino acids (K(d) = 5.6 nM). The data indicate that immature 3CL(pro) can form dimer enabling it to undergo autoprocessing to yield the mature enzyme, which further serves as a seed for facilitated maturation. Taken together, this study provides insights into the maturation process of the SARS 3CL(pro) from the polyprotein and design of new structure-based inhibitors.
About this Structure
1Z1J is a Single protein structure of sequence from Human sars coronavirus. Full crystallographic information is available from OCA.
Reference
Mechanism of the maturation process of SARS-CoV 3CL protease., Hsu MF, Kuo CJ, Chang KT, Chang HC, Chou CC, Ko TP, Shr HL, Chang GG, Wang AH, Liang PH, J Biol Chem. 2005 Sep 2;280(35):31257-66. Epub 2005 Mar 23. PMID:15788388 Page seeded by OCA on Sat May 3 17:04:38 2008
