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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
21
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pubmed:dateCreated |
2008-10-22
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pubmed:abstractText |
The 3C-like (3CL) protease of the severe acute respiratory syndrome (SARS) coronavirus is a key enzyme for the virus maturation. We found for the first time that the mature SARS 3CL protease is subject to degradation at 188Arg/189Gln. Replacing Arg with Ile at position 188 rendered the protease resistant to proteolysis. The R188I mutant digested a conserved undecapeptide substrate with a K(m) of 33.8 microM and k(cat) of 4753 s(-1). Compared with the value reported for the mature protease containing a C-terminal His-tag, the relative activity of the mutant was nearly 10(6). Novel peptide-aldehyde derivatives containing a side-chain-protected C-terminal Gln efficiently inhibited the catalytic activity of the R188I mutant. The results indicated for the first time that the tetrapeptide sequence is enough for inhibitory activities of peptide-aldehyde derivatives.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1464-3391
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9400-8
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pubmed:meshHeading |
pubmed-meshheading:18845442-Aldehydes,
pubmed-meshheading:18845442-Amino Acid Sequence,
pubmed-meshheading:18845442-Binding Sites,
pubmed-meshheading:18845442-Cysteine Endopeptidases,
pubmed-meshheading:18845442-Humans,
pubmed-meshheading:18845442-Hydrolysis,
pubmed-meshheading:18845442-Models, Molecular,
pubmed-meshheading:18845442-Molecular Sequence Data,
pubmed-meshheading:18845442-Molecular Structure,
pubmed-meshheading:18845442-Mutation,
pubmed-meshheading:18845442-Protease Inhibitors,
pubmed-meshheading:18845442-Protein Conformation,
pubmed-meshheading:18845442-Protein Processing, Post-Translational,
pubmed-meshheading:18845442-SARS Virus,
pubmed-meshheading:18845442-Severe Acute Respiratory Syndrome,
pubmed-meshheading:18845442-Spectrometry, Mass, Matrix-Assisted Laser...,
pubmed-meshheading:18845442-Substrate Specificity,
pubmed-meshheading:18845442-Viral Proteins
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pubmed:year |
2008
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pubmed:articleTitle |
Evaluation of peptide-aldehyde inhibitors using R188I mutant of SARS 3CL protease as a proteolysis-resistant mutant.
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pubmed:affiliation |
Department of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kita-ku, Kyoto 603-8334, Japan. akaji@koto.kpu-m.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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