Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris.
Identifieur interne : 001D21 ( Main/Exploration ); précédent : 001D20; suivant : 001D22Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris.
Auteurs : Thi Thanh Hanh Nguyen [Corée du Sud] ; Hye-Jin Woo ; Hee-Kyoung Kang ; Van Dao Nguyen ; Young-Min Kim ; Do-Won Kim ; Sul-Ah Ahn ; Yongmei Xia ; Doman KimSource :
- Biotechnology letters [ 1573-6776 ] ; 2012.
Descripteurs français
- KwdFr :
- Catéchine (analogues et dérivés), Catéchine (métabolisme), Cinétique, Concentration inhibitrice 50, Cysteine endopeptidases (), Cysteine endopeptidases (biosynthèse), Cysteine endopeptidases (génétique), Expression des gènes, Flavonoïdes (métabolisme), Hydrolyse, Inhibiteurs de protéases (métabolisme), Masse moléculaire, Pichia (génétique), Protéines recombinantes (), Protéines recombinantes (antagonistes et inhibiteurs), Protéines recombinantes (biosynthèse), Protéines recombinantes (génétique), Protéines virales (), Protéines virales (antagonistes et inhibiteurs), Protéines virales (biosynthèse), Protéines virales (génétique), Virus du SRAS (enzymologie), Virus du SRAS (génétique).
- MESH :
- analogues et dérivés : Catéchine.
- antagonistes et inhibiteurs : Protéines recombinantes, Protéines virales.
- biosynthèse : Cysteine endopeptidases, Protéines recombinantes, Protéines virales.
- enzymologie : Virus du SRAS.
- génétique : Cysteine endopeptidases, Pichia, Protéines recombinantes, Protéines virales, Virus du SRAS.
- métabolisme : Catéchine, Flavonoïdes, Inhibiteurs de protéases.
- Cinétique, Concentration inhibitrice 50, Cysteine endopeptidases, Expression des gènes, Hydrolyse, Masse moléculaire, Protéines recombinantes, Protéines virales.
English descriptors
- KwdEn :
- Catechin (analogs & derivatives), Catechin (metabolism), Cysteine Endopeptidases (biosynthesis), Cysteine Endopeptidases (chemistry), Cysteine Endopeptidases (genetics), Flavonoids (metabolism), Gene Expression, Hydrolysis, Inhibitory Concentration 50, Kinetics, Molecular Weight, Pichia (genetics), Protease Inhibitors (metabolism), Recombinant Proteins (antagonists & inhibitors), Recombinant Proteins (biosynthesis), Recombinant Proteins (chemistry), Recombinant Proteins (genetics), SARS Virus (enzymology), SARS Virus (genetics), Viral Proteins (antagonists & inhibitors), Viral Proteins (biosynthesis), Viral Proteins (chemistry), Viral Proteins (genetics).
- MESH :
- chemical , analogs & derivatives : Catechin.
- chemical , antagonists & inhibitors : Recombinant Proteins, Viral Proteins.
- chemical , biosynthesis : Cysteine Endopeptidases, Recombinant Proteins, Viral Proteins.
- chemical , chemistry : Cysteine Endopeptidases, Recombinant Proteins, Viral Proteins.
- chemical , genetics : Cysteine Endopeptidases, Recombinant Proteins, Viral Proteins.
- chemical , metabolism : Catechin, Flavonoids, Protease Inhibitors.
- enzymology : SARS Virus.
- genetics : Pichia, SARS Virus.
- Gene Expression, Hydrolysis, Inhibitory Concentration 50, Kinetics, Molecular Weight.
Abstract
The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Recombinant 3CL(pro) was expressed in Pichia pastoris GS115 as a 42 kDa protein that displayed a K ( m ) of 15 ± 2 μM with Dabcyl-KTSAVLQSGFRKME-Edans as substrate. Purified 3CL(pro) was used for inhibition and kinetic assays with seven flavonoid compounds. The IC(50) of six flavonoid compounds were 47-381 μM. Quercetin, epigallocatechin gallate and gallocatechin gallate (GCG) displayed good inhibition toward 3CL(pro) with IC(50) values of 73, 73 and 47 μM, respectively. GCG showed a competitive inhibition pattern with K ( i ) value of 25 ± 1.7 μM. In molecular docking experiments, GCG displayed a binding energy of -14 kcal mol(-1) to the active site of 3CL(pro) and the galloyl moiety at 3-OH position was required for 3CL(pro) inhibition activity.
DOI: 10.1007/s10529-011-0845-8
PubMed: 22350287
Affiliations:
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Le document en format XML
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Woo</name></author><author><name sortKey="Kang, Hee Kyoung" sort="Kang, Hee Kyoung" uniqKey="Kang H" first="Hee-Kyoung" last="Kang">Hee-Kyoung Kang</name></author><author><name sortKey="Nguyen, Van Dao" sort="Nguyen, Van Dao" uniqKey="Nguyen V" first="Van Dao" last="Nguyen">Van Dao Nguyen</name></author><author><name sortKey="Kim, Young Min" sort="Kim, Young Min" uniqKey="Kim Y" first="Young-Min" last="Kim">Young-Min Kim</name></author><author><name sortKey="Kim, Do Won" sort="Kim, Do Won" uniqKey="Kim D" first="Do-Won" last="Kim">Do-Won Kim</name></author><author><name sortKey="Ahn, Sul Ah" sort="Ahn, Sul Ah" uniqKey="Ahn S" first="Sul-Ah" last="Ahn">Sul-Ah Ahn</name></author><author><name sortKey="Xia, Yongmei" sort="Xia, Yongmei" uniqKey="Xia Y" first="Yongmei" last="Xia">Yongmei Xia</name></author><author><name sortKey="Kim, Doman" sort="Kim, Doman" uniqKey="Kim D" first="Doman" last="Kim">Doman Kim</name></author></titleStmt><publicationStmt><idno 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xml:lang="en">Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris.</title><author><name sortKey="Nguyen, Thi Thanh Hanh" sort="Nguyen, Thi Thanh Hanh" uniqKey="Nguyen T" first="Thi Thanh Hanh" last="Nguyen">Thi Thanh Hanh Nguyen</name><affiliation wicri:level="1"><nlm:affiliation>School of Biological Sciences and Technology and the Research Institute for Catalysis, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 500-757, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>School of Biological Sciences and Technology and the Research Institute for Catalysis, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 500-757</wicri:regionArea><wicri:noRegion>500-757</wicri:noRegion></affiliation></author><author><name sortKey="Woo, Hye Jin" sort="Woo, Hye Jin" uniqKey="Woo H" first="Hye-Jin" last="Woo">Hye-Jin Woo</name></author><author><name sortKey="Kang, Hee Kyoung" sort="Kang, Hee Kyoung" uniqKey="Kang H" first="Hee-Kyoung" last="Kang">Hee-Kyoung Kang</name></author><author><name sortKey="Nguyen, Van Dao" sort="Nguyen, Van Dao" uniqKey="Nguyen V" first="Van Dao" last="Nguyen">Van Dao Nguyen</name></author><author><name sortKey="Kim, Young Min" sort="Kim, Young Min" uniqKey="Kim Y" first="Young-Min" last="Kim">Young-Min Kim</name></author><author><name sortKey="Kim, Do Won" sort="Kim, Do Won" uniqKey="Kim D" first="Do-Won" last="Kim">Do-Won Kim</name></author><author><name sortKey="Ahn, Sul Ah" sort="Ahn, Sul Ah" uniqKey="Ahn S" first="Sul-Ah" last="Ahn">Sul-Ah Ahn</name></author><author><name sortKey="Xia, Yongmei" sort="Xia, Yongmei" uniqKey="Xia Y" first="Yongmei" last="Xia">Yongmei Xia</name></author><author><name sortKey="Kim, Doman" sort="Kim, Doman" uniqKey="Kim D" first="Doman" last="Kim">Doman Kim</name></author></analytic><series><title level="j">Biotechnology letters</title><idno type="eISSN">1573-6776</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Catechin (analogs & derivatives)</term><term>Catechin (metabolism)</term><term>Cysteine Endopeptidases (biosynthesis)</term><term>Cysteine Endopeptidases (chemistry)</term><term>Cysteine Endopeptidases (genetics)</term><term>Flavonoids (metabolism)</term><term>Gene Expression</term><term>Hydrolysis</term><term>Inhibitory Concentration 50</term><term>Kinetics</term><term>Molecular Weight</term><term>Pichia (genetics)</term><term>Protease Inhibitors (metabolism)</term><term>Recombinant Proteins (antagonists & inhibitors)</term><term>Recombinant Proteins (biosynthesis)</term><term>Recombinant Proteins (chemistry)</term><term>Recombinant Proteins (genetics)</term><term>SARS Virus (enzymology)</term><term>SARS Virus (genetics)</term><term>Viral Proteins (antagonists & inhibitors)</term><term>Viral Proteins (biosynthesis)</term><term>Viral Proteins (chemistry)</term><term>Viral Proteins (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Catéchine (analogues et dérivés)</term><term>Catéchine (métabolisme)</term><term>Cinétique</term><term>Concentration inhibitrice 50</term><term>Cysteine endopeptidases ()</term><term>Cysteine endopeptidases (biosynthèse)</term><term>Cysteine endopeptidases (génétique)</term><term>Expression des gènes</term><term>Flavonoïdes (métabolisme)</term><term>Hydrolyse</term><term>Inhibiteurs de protéases (métabolisme)</term><term>Masse moléculaire</term><term>Pichia (génétique)</term><term>Protéines recombinantes ()</term><term>Protéines recombinantes (antagonistes et inhibiteurs)</term><term>Protéines recombinantes (biosynthèse)</term><term>Protéines recombinantes (génétique)</term><term>Protéines virales ()</term><term>Protéines virales (antagonistes et inhibiteurs)</term><term>Protéines virales (biosynthèse)</term><term>Protéines virales (génétique)</term><term>Virus du SRAS (enzymologie)</term><term>Virus du SRAS (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Catechin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Recombinant Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Cysteine Endopeptidases</term><term>Recombinant Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Cysteine Endopeptidases</term><term>Recombinant Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cysteine Endopeptidases</term><term>Recombinant Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Catechin</term><term>Flavonoids</term><term>Protease Inhibitors</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Catéchine</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines recombinantes</term><term>Protéines virales</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Cysteine endopeptidases</term><term>Protéines recombinantes</term><term>Protéines virales</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Pichia</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Cysteine endopeptidases</term><term>Pichia</term><term>Protéines recombinantes</term><term>Protéines virales</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Catéchine</term><term>Flavonoïdes</term><term>Inhibiteurs de protéases</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Gene Expression</term><term>Hydrolysis</term><term>Inhibitory Concentration 50</term><term>Kinetics</term><term>Molecular Weight</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cinétique</term><term>Concentration inhibitrice 50</term><term>Cysteine endopeptidases</term><term>Expression des gènes</term><term>Hydrolyse</term><term>Masse moléculaire</term><term>Protéines recombinantes</term><term>Protéines virales</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Recombinant 3CL(pro) was expressed in Pichia pastoris GS115 as a 42 kDa protein that displayed a K ( m ) of 15 ± 2 μM with Dabcyl-KTSAVLQSGFRKME-Edans as substrate. Purified 3CL(pro) was used for inhibition and kinetic assays with seven flavonoid compounds. The IC(50) of six flavonoid compounds were 47-381 μM. Quercetin, epigallocatechin gallate and gallocatechin gallate (GCG) displayed good inhibition toward 3CL(pro) with IC(50) values of 73, 73 and 47 μM, respectively. GCG showed a competitive inhibition pattern with K ( i ) value of 25 ± 1.7 μM. In molecular docking experiments, GCG displayed a binding energy of -14 kcal mol(-1) to the active site of 3CL(pro) and the galloyl moiety at 3-OH position was required for 3CL(pro) inhibition activity.</div></front></TEI><affiliations><list><country><li>Corée du Sud</li></country></list><tree><noCountry><name sortKey="Ahn, Sul Ah" sort="Ahn, Sul Ah" uniqKey="Ahn S" first="Sul-Ah" last="Ahn">Sul-Ah Ahn</name><name sortKey="Kang, Hee Kyoung" sort="Kang, Hee Kyoung" uniqKey="Kang H" first="Hee-Kyoung" last="Kang">Hee-Kyoung Kang</name><name sortKey="Kim, Do Won" sort="Kim, Do Won" uniqKey="Kim D" first="Do-Won" last="Kim">Do-Won Kim</name><name sortKey="Kim, Doman" sort="Kim, Doman" uniqKey="Kim D" first="Doman" last="Kim">Doman Kim</name><name sortKey="Kim, Young Min" sort="Kim, Young Min" uniqKey="Kim Y" first="Young-Min" last="Kim">Young-Min Kim</name><name sortKey="Nguyen, Van Dao" sort="Nguyen, Van Dao" uniqKey="Nguyen V" first="Van Dao" last="Nguyen">Van Dao Nguyen</name><name sortKey="Woo, Hye Jin" sort="Woo, Hye Jin" uniqKey="Woo H" first="Hye-Jin" last="Woo">Hye-Jin Woo</name><name sortKey="Xia, Yongmei" sort="Xia, Yongmei" uniqKey="Xia Y" first="Yongmei" last="Xia">Yongmei Xia</name></noCountry><country name="Corée du Sud"><noRegion><name sortKey="Nguyen, Thi Thanh Hanh" sort="Nguyen, Thi Thanh Hanh" uniqKey="Nguyen T" first="Thi Thanh Hanh" last="Nguyen">Thi Thanh Hanh Nguyen</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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