Evaluation of peptide-aldehyde inhibitors using R188I mutant of SARS 3CL protease as a proteolysis-resistant mutant
Identifieur interne : 000237 ( PascalFrancis/Corpus ); précédent : 000236; suivant : 000238Evaluation of peptide-aldehyde inhibitors using R188I mutant of SARS 3CL protease as a proteolysis-resistant mutant
Auteurs : Kenichi Akaji ; Hiroyuki Konno ; Mari Onozuka ; Ayumi Makino ; Hiroyuki Saito ; Kazuto NosakaSource :
- Bioorganic & medicinal chemistry [ 0968-0896 ] ; 2008.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
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 lle at position 188 rendered the protease resistant to proteolysis. The R188I mutant digested a conserved undecapeptide substrate with a Km of 33.8 μM and kcat 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 106. 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.
Notice en format standard (ISO 2709)
Pour connaître la documentation sur le format Inist Standard.
pA |
|
---|
Format Inist (serveur)
NO : | PASCAL 09-0041831 INIST |
---|---|
ET : | Evaluation of peptide-aldehyde inhibitors using R188I mutant of SARS 3CL protease as a proteolysis-resistant mutant |
AU : | AKAJI (Kenichi); KONNO (Hiroyuki); ONOZUKA (Mari); MAKINO (Ayumi); SAITO (Hiroyuki); NOSAKA (Kazuto) |
AF : | Department of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine/Kita-ku, Kyoto 603-8334/Japon (1 aut., 2 aut., 3 aut., 6 aut.); Department of Biophysical Chemistry, Kobe Pharmaceutical University/Kobe 658-8558/Japon (4 aut., 5 aut.) |
DT : | Publication en série; Niveau analytique |
SO : | Bioorganic & medicinal chemistry; ISSN 0968-0896; Royaume-Uni; Da. 2008; Vol. 16; No. 21; Pp. 9400-9408 |
LA : | Anglais |
EA : | 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 lle at position 188 rendered the protease resistant to proteolysis. The R188I mutant digested a conserved undecapeptide substrate with a Km of 33.8 μM and kcat 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 106. 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. |
CC : | 002B02S05 |
FD : | Peptide; Aldéhyde; Inhibiteur protease; Mutation; Cysteine endopeptidases; Virus syndrome respiratoire aigu sévère; Résistance hydrolyse; Activité biologique; Synthèse chimique; Synthèse peptidique; In vitro; Inhibiteur enzyme; Glutamique acide(acétylthréonyl-séryl-alanyl-valyl-leucyl-1-désoxy) |
FG : | Peptidases; Hydrolases; Enzyme; Coronavirus; Coronaviridae; Nidovirales; Virus |
ED : | Peptides; Aldehyde; Protease inhibitor; Mutation; Cysteine endopeptidases; Severe acute respiratory syndrome virus; Hydrolysis resistance; Biological activity; Chemical synthesis; Peptide synthesis; In vitro; Enzyme inhibitor |
EG : | Peptidases; Hydrolases; Enzyme; Coronavirus; Coronaviridae; Nidovirales; Virus |
SD : | Péptido; Aldehído; Inhibidor proteasa; Mutación; Cysteine endopeptidases; Severe acute respiratory syndrome virus; Resistencia hidrólisis; Actividad biológica; Síntesis química; Síntesis peptídica; In vitro; Inhibidor enzima |
LO : | INIST-26564.354000185936900010 |
ID : | 09-0041831 |
Links to Exploration step
Pascal:09-0041831Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Evaluation of peptide-aldehyde inhibitors using R188I mutant of SARS 3CL protease as a proteolysis-resistant mutant</title>
<author><name sortKey="Akaji, Kenichi" sort="Akaji, Kenichi" uniqKey="Akaji K" first="Kenichi" last="Akaji">Kenichi Akaji</name>
<affiliation><inist:fA14 i1="01"><s1>Department of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine</s1>
<s2>Kita-ku, Kyoto 603-8334</s2>
<s3>JPN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Konno, Hiroyuki" sort="Konno, Hiroyuki" uniqKey="Konno H" first="Hiroyuki" last="Konno">Hiroyuki Konno</name>
<affiliation><inist:fA14 i1="01"><s1>Department of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine</s1>
<s2>Kita-ku, Kyoto 603-8334</s2>
<s3>JPN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Onozuka, Mari" sort="Onozuka, Mari" uniqKey="Onozuka M" first="Mari" last="Onozuka">Mari Onozuka</name>
<affiliation><inist:fA14 i1="01"><s1>Department of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine</s1>
<s2>Kita-ku, Kyoto 603-8334</s2>
<s3>JPN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Makino, Ayumi" sort="Makino, Ayumi" uniqKey="Makino A" first="Ayumi" last="Makino">Ayumi Makino</name>
<affiliation><inist:fA14 i1="02"><s1>Department of Biophysical Chemistry, Kobe Pharmaceutical University</s1>
<s2>Kobe 658-8558</s2>
<s3>JPN</s3>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Saito, Hiroyuki" sort="Saito, Hiroyuki" uniqKey="Saito H" first="Hiroyuki" last="Saito">Hiroyuki Saito</name>
<affiliation><inist:fA14 i1="02"><s1>Department of Biophysical Chemistry, Kobe Pharmaceutical University</s1>
<s2>Kobe 658-8558</s2>
<s3>JPN</s3>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Nosaka, Kazuto" sort="Nosaka, Kazuto" uniqKey="Nosaka K" first="Kazuto" last="Nosaka">Kazuto Nosaka</name>
<affiliation><inist:fA14 i1="01"><s1>Department of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine</s1>
<s2>Kita-ku, Kyoto 603-8334</s2>
<s3>JPN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">INIST</idno>
<idno type="inist">09-0041831</idno>
<date when="2008">2008</date>
<idno type="stanalyst">PASCAL 09-0041831 INIST</idno>
<idno type="RBID">Pascal:09-0041831</idno>
<idno type="wicri:Area/PascalFrancis/Corpus">000237</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Evaluation of peptide-aldehyde inhibitors using R188I mutant of SARS 3CL protease as a proteolysis-resistant mutant</title>
<author><name sortKey="Akaji, Kenichi" sort="Akaji, Kenichi" uniqKey="Akaji K" first="Kenichi" last="Akaji">Kenichi Akaji</name>
<affiliation><inist:fA14 i1="01"><s1>Department of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine</s1>
<s2>Kita-ku, Kyoto 603-8334</s2>
<s3>JPN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Konno, Hiroyuki" sort="Konno, Hiroyuki" uniqKey="Konno H" first="Hiroyuki" last="Konno">Hiroyuki Konno</name>
<affiliation><inist:fA14 i1="01"><s1>Department of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine</s1>
<s2>Kita-ku, Kyoto 603-8334</s2>
<s3>JPN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Onozuka, Mari" sort="Onozuka, Mari" uniqKey="Onozuka M" first="Mari" last="Onozuka">Mari Onozuka</name>
<affiliation><inist:fA14 i1="01"><s1>Department of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine</s1>
<s2>Kita-ku, Kyoto 603-8334</s2>
<s3>JPN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Makino, Ayumi" sort="Makino, Ayumi" uniqKey="Makino A" first="Ayumi" last="Makino">Ayumi Makino</name>
<affiliation><inist:fA14 i1="02"><s1>Department of Biophysical Chemistry, Kobe Pharmaceutical University</s1>
<s2>Kobe 658-8558</s2>
<s3>JPN</s3>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Saito, Hiroyuki" sort="Saito, Hiroyuki" uniqKey="Saito H" first="Hiroyuki" last="Saito">Hiroyuki Saito</name>
<affiliation><inist:fA14 i1="02"><s1>Department of Biophysical Chemistry, Kobe Pharmaceutical University</s1>
<s2>Kobe 658-8558</s2>
<s3>JPN</s3>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Nosaka, Kazuto" sort="Nosaka, Kazuto" uniqKey="Nosaka K" first="Kazuto" last="Nosaka">Kazuto Nosaka</name>
<affiliation><inist:fA14 i1="01"><s1>Department of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine</s1>
<s2>Kita-ku, Kyoto 603-8334</s2>
<s3>JPN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Bioorganic & medicinal chemistry</title>
<title level="j" type="abbreviated">Bioorg. med. chem.</title>
<idno type="ISSN">0968-0896</idno>
<imprint><date when="2008">2008</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Bioorganic & medicinal chemistry</title>
<title level="j" type="abbreviated">Bioorg. med. chem.</title>
<idno type="ISSN">0968-0896</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aldehyde</term>
<term>Biological activity</term>
<term>Chemical synthesis</term>
<term>Cysteine endopeptidases</term>
<term>Enzyme inhibitor</term>
<term>Hydrolysis resistance</term>
<term>In vitro</term>
<term>Mutation</term>
<term>Peptide synthesis</term>
<term>Peptides</term>
<term>Protease inhibitor</term>
<term>Severe acute respiratory syndrome virus</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Peptide</term>
<term>Aldéhyde</term>
<term>Inhibiteur protease</term>
<term>Mutation</term>
<term>Cysteine endopeptidases</term>
<term>Virus syndrome respiratoire aigu sévère</term>
<term>Résistance hydrolyse</term>
<term>Activité biologique</term>
<term>Synthèse chimique</term>
<term>Synthèse peptidique</term>
<term>In vitro</term>
<term>Inhibiteur enzyme</term>
<term>Glutamique acide(acétylthréonyl-séryl-alanyl-valyl-leucyl-1-désoxy)</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">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 lle at position 188 rendered the protease resistant to proteolysis. The R188I mutant digested a conserved undecapeptide substrate with a K<sub>m</sub>
of 33.8 μM and k<sub>cat</sub>
of 4753 s<sup>-1</sup>
. Compared with the value reported for the mature protease containing a C-terminal His-tag, the relative activity of the mutant was nearly 10<sup>6</sup>
. 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.</div>
</front>
</TEI>
<inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0968-0896</s0>
</fA01>
<fA03 i2="1"><s0>Bioorg. med. chem.</s0>
</fA03>
<fA05><s2>16</s2>
</fA05>
<fA06><s2>21</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG"><s1>Evaluation of peptide-aldehyde inhibitors using R188I mutant of SARS 3CL protease as a proteolysis-resistant mutant</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>AKAJI (Kenichi)</s1>
</fA11>
<fA11 i1="02" i2="1"><s1>KONNO (Hiroyuki)</s1>
</fA11>
<fA11 i1="03" i2="1"><s1>ONOZUKA (Mari)</s1>
</fA11>
<fA11 i1="04" i2="1"><s1>MAKINO (Ayumi)</s1>
</fA11>
<fA11 i1="05" i2="1"><s1>SAITO (Hiroyuki)</s1>
</fA11>
<fA11 i1="06" i2="1"><s1>NOSAKA (Kazuto)</s1>
</fA11>
<fA14 i1="01"><s1>Department of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine</s1>
<s2>Kita-ku, Kyoto 603-8334</s2>
<s3>JPN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
</fA14>
<fA14 i1="02"><s1>Department of Biophysical Chemistry, Kobe Pharmaceutical University</s1>
<s2>Kobe 658-8558</s2>
<s3>JPN</s3>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
</fA14>
<fA20><s1>9400-9408</s1>
</fA20>
<fA21><s1>2008</s1>
</fA21>
<fA23 i1="01"><s0>ENG</s0>
</fA23>
<fA43 i1="01"><s1>INIST</s1>
<s2>26564</s2>
<s5>354000185936900010</s5>
</fA43>
<fA44><s0>0000</s0>
<s1>© 2009 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA47 i1="01" i2="1"><s0>09-0041831</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Bioorganic & medicinal chemistry</s0>
</fA64>
<fA66 i1="01"><s0>GBR</s0>
</fA66>
<fA99><s0>1/2 p.ref. et notes</s0>
</fA99>
<fC01 i1="01" l="ENG"><s0>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 lle at position 188 rendered the protease resistant to proteolysis. The R188I mutant digested a conserved undecapeptide substrate with a K<sub>m</sub>
of 33.8 μM and k<sub>cat</sub>
of 4753 s<sup>-1</sup>
. Compared with the value reported for the mature protease containing a C-terminal His-tag, the relative activity of the mutant was nearly 10<sup>6</sup>
. 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.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B02S05</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Peptide</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Peptides</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Péptido</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Aldéhyde</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Aldehyde</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Aldehído</s0>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Inhibiteur protease</s0>
<s2>FR</s2>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Protease inhibitor</s0>
<s2>FR</s2>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Inhibidor proteasa</s0>
<s2>FR</s2>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Mutation</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Mutation</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Mutación</s0>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Cysteine endopeptidases</s0>
<s2>FE</s2>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Cysteine endopeptidases</s0>
<s2>FE</s2>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Cysteine endopeptidases</s0>
<s2>FE</s2>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Virus syndrome respiratoire aigu sévère</s0>
<s2>NW</s2>
<s5>07</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Severe acute respiratory syndrome virus</s0>
<s2>NW</s2>
<s5>07</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Severe acute respiratory syndrome virus</s0>
<s2>NW</s2>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Résistance hydrolyse</s0>
<s5>08</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Hydrolysis resistance</s0>
<s5>08</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA"><s0>Resistencia hidrólisis</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Activité biologique</s0>
<s5>09</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG"><s0>Biological activity</s0>
<s5>09</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Actividad biológica</s0>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE"><s0>Synthèse chimique</s0>
<s5>10</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG"><s0>Chemical synthesis</s0>
<s5>10</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA"><s0>Síntesis química</s0>
<s5>10</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE"><s0>Synthèse peptidique</s0>
<s5>11</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG"><s0>Peptide synthesis</s0>
<s5>11</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA"><s0>Síntesis peptídica</s0>
<s5>11</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE"><s0>In vitro</s0>
<s5>12</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG"><s0>In vitro</s0>
<s5>12</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA"><s0>In vitro</s0>
<s5>12</s5>
</fC03>
<fC03 i1="12" i2="X" l="FRE"><s0>Inhibiteur enzyme</s0>
<s5>32</s5>
</fC03>
<fC03 i1="12" i2="X" l="ENG"><s0>Enzyme inhibitor</s0>
<s5>32</s5>
</fC03>
<fC03 i1="12" i2="X" l="SPA"><s0>Inhibidor enzima</s0>
<s5>32</s5>
</fC03>
<fC03 i1="13" i2="X" l="FRE"><s0>Glutamique acide(acétylthréonyl-séryl-alanyl-valyl-leucyl-1-désoxy)</s0>
<s4>INC</s4>
<s5>76</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Peptidases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Peptidases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Peptidases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Hydrolases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Hydrolases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Hydrolases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Enzima</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Coronavirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Coronavirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Coronavirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fN21><s1>026</s1>
</fN21>
</pA>
</standard>
<server><NO>PASCAL 09-0041831 INIST</NO>
<ET>Evaluation of peptide-aldehyde inhibitors using R188I mutant of SARS 3CL protease as a proteolysis-resistant mutant</ET>
<AU>AKAJI (Kenichi); KONNO (Hiroyuki); ONOZUKA (Mari); MAKINO (Ayumi); SAITO (Hiroyuki); NOSAKA (Kazuto)</AU>
<AF>Department of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine/Kita-ku, Kyoto 603-8334/Japon (1 aut., 2 aut., 3 aut., 6 aut.); Department of Biophysical Chemistry, Kobe Pharmaceutical University/Kobe 658-8558/Japon (4 aut., 5 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Bioorganic & medicinal chemistry; ISSN 0968-0896; Royaume-Uni; Da. 2008; Vol. 16; No. 21; Pp. 9400-9408</SO>
<LA>Anglais</LA>
<EA>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 lle at position 188 rendered the protease resistant to proteolysis. The R188I mutant digested a conserved undecapeptide substrate with a K<sub>m</sub>
of 33.8 μM and k<sub>cat</sub>
of 4753 s<sup>-1</sup>
. Compared with the value reported for the mature protease containing a C-terminal His-tag, the relative activity of the mutant was nearly 10<sup>6</sup>
. 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.</EA>
<CC>002B02S05</CC>
<FD>Peptide; Aldéhyde; Inhibiteur protease; Mutation; Cysteine endopeptidases; Virus syndrome respiratoire aigu sévère; Résistance hydrolyse; Activité biologique; Synthèse chimique; Synthèse peptidique; In vitro; Inhibiteur enzyme; Glutamique acide(acétylthréonyl-séryl-alanyl-valyl-leucyl-1-désoxy)</FD>
<FG>Peptidases; Hydrolases; Enzyme; Coronavirus; Coronaviridae; Nidovirales; Virus</FG>
<ED>Peptides; Aldehyde; Protease inhibitor; Mutation; Cysteine endopeptidases; Severe acute respiratory syndrome virus; Hydrolysis resistance; Biological activity; Chemical synthesis; Peptide synthesis; In vitro; Enzyme inhibitor</ED>
<EG>Peptidases; Hydrolases; Enzyme; Coronavirus; Coronaviridae; Nidovirales; Virus</EG>
<SD>Péptido; Aldehído; Inhibidor proteasa; Mutación; Cysteine endopeptidases; Severe acute respiratory syndrome virus; Resistencia hidrólisis; Actividad biológica; Síntesis química; Síntesis peptídica; In vitro; Inhibidor enzima</SD>
<LO>INIST-26564.354000185936900010</LO>
<ID>09-0041831</ID>
</server>
</inist>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/PascalFrancis/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000237 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PascalFrancis/Corpus/biblio.hfd -nk 000237 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= SrasV1 |flux= PascalFrancis |étape= Corpus |type= RBID |clé= Pascal:09-0041831 |texte= Evaluation of peptide-aldehyde inhibitors using R188I mutant of SARS 3CL protease as a proteolysis-resistant mutant }}
![]() | This area was generated with Dilib version V0.6.33. | ![]() |