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PDBsum entry 2vj1
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References listed in PDB file
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Key reference
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Title
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A structural view of the inactivation of the sars coronavirus main proteinase by benzotriazole esters.
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Authors
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K.H.Verschueren,
K.Pumpor,
S.Anemüller,
S.Chen,
J.R.Mesters,
R.Hilgenfeld.
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Ref.
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Chem Biol, 2008,
15,
597-606.
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PubMed id
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Abstract
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The main proteinase (M(pro)) of the severe acute respiratory syndrome (SARS)
coronavirus is a principal target for the design of anticoronaviral compounds.
Benzotriazole esters have been reported as potent nonpeptidic inhibitors of the
enzyme, but their exact mechanism of action remains unclear. Here we present
crystal structures of SARS-CoV M(pro), the active-site cysteine of which has
been acylated by benzotriazole esters that act as suicide inhibitors. In one of
the structures, the thioester product has been hydrolyzed and benzoic acid is
observed to bind to the hydrophobic S2 pocket. This structure also features the
enzyme with a shortened N-terminal segment ("amputated N finger"). The results
further the understanding of the important role of the N finger for catalysis as
well as the design of benzotriazole inhibitors with improved specificity.
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