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PDBsum entry 3f9e
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References listed in PDB file
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Key reference
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Title
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Two adjacent mutations on the dimer interface of sars coronavirus 3c-Like protease cause different conformational changes in crystal structure.
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Authors
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T.Hu,
Y.Zhang,
L.Li,
K.Wang,
S.Chen,
J.Chen,
J.Ding,
H.Jiang,
X.Shen.
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Ref.
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Virology, 2009,
388,
324-334.
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PubMed id
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Abstract
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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).
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