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PDBsum entry 3d23
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Hydrolase/hydrolase inhibitor
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PDB id
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3d23
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References listed in PDB file
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Key reference
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Title
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Structure of the main protease from a global infectious human coronavirus, Hcov-Hku1.
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Authors
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Q.Zhao,
S.Li,
F.Xue,
Y.Zou,
C.Chen,
M.Bartlam,
Z.Rao.
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Ref.
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J Virol, 2008,
82,
8647-8655.
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PubMed id
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Abstract
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The newly emergent human coronavirus HKU1 (HCoV-HKU1) was first identified in
Hong Kong in 2005. Infection by HCoV-HKU1 occurs worldwide and causes syndromes
such as the common cold, bronchitis, and pneumonia. The CoV main protease
(M(pro)), which is a key enzyme in viral replication via the proteolytic
processing of the replicase polyproteins, has been recognized as an attractive
target for rational drug design. In this study, we report the structure of
HCoV-HKU1 M(pro) in complex with a Michael acceptor, inhibitor N3. The structure
of HCoV-HKU1 provides a high-quality model for group 2A CoVs, which are distinct
from group 2B CoVs such as severe acute respiratory syndrome CoV. The structure,
together with activity assays, supports the relative conservation at the P1
position that was discovered by sequencing the HCoV-HKU1 genome. Combined with
structural data from other CoV M(pro)s, the HCoV-HKU1 M(pro) structure reported
here provides insights into both substrate preference and the design of
antivirals targeting CoVs.
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