The effects and mechanism of flavonoid-rePON1 interactions. Structure-activity relationship study.
Identifieur interne : 001053 ( Main/Exploration ); précédent : 001052; suivant : 001054The effects and mechanism of flavonoid-rePON1 interactions. Structure-activity relationship study.
Auteurs : Dana Atrahimovich [Israël] ; Jacob Vaya ; Soliman KhatibSource :
- Bioorganic & medicinal chemistry [ 1464-3391 ] ; 2013.
Descripteurs français
- KwdFr :
- Aryldialkylphosphatase (), Conformation des protéines, Cuivre (), Flavonoïdes (), Humains, Liaison aux protéines, Lipoprotéines HDL (), Lipoprotéines LDL (), Oxydoréduction, Protéines recombinantes (), Relation structure-activité, Simulation de docking moléculaire, Site allostérique, Spectrométrie de fluorescence, Tryptophane ().
- MESH :
- Aryldialkylphosphatase, Conformation des protéines, Cuivre, Flavonoïdes, Humains, Liaison aux protéines, Lipoprotéines HDL, Lipoprotéines LDL, Oxydoréduction, Protéines recombinantes, Relation structure-activité, Simulation de docking moléculaire, Site allostérique, Spectrométrie de fluorescence, Tryptophane.
English descriptors
- KwdEn :
- Allosteric Site, Aryldialkylphosphatase (chemistry), Copper (chemistry), Flavonoids (chemistry), Humans, Lipoproteins, HDL (chemistry), Lipoproteins, LDL (chemistry), Molecular Docking Simulation, Oxidation-Reduction, Protein Binding, Protein Conformation, Recombinant Proteins (chemistry), Spectrometry, Fluorescence, Structure-Activity Relationship, Tryptophan (chemistry).
- MESH :
- chemical , chemistry : Aryldialkylphosphatase, Copper, Flavonoids, Lipoproteins, HDL, Lipoproteins, LDL, Recombinant Proteins, Tryptophan.
- Allosteric Site, Humans, Molecular Docking Simulation, Oxidation-Reduction, Protein Binding, Protein Conformation, Spectrometry, Fluorescence, Structure-Activity Relationship.
Abstract
Flavonoids are plant phenolic secondary metabolites that are widely distributed in the human diet. These antioxidants have received much attention because of their neuroprotective, cardioprotective, and chemopreventive actions. While a major focus has been on the flavonoids' antioxidant properties, there is an emerging view that many of the potential health benefits of flavonoids and their in vivo metabolites are due to modulatory actions in cells through direct interactions with proteins, and not necessarily due to their antioxidant function. This view relies on the observations that flavonoids are present in the circulation at very low concentrations, which are not sufficient to exert effective antioxidant effects. The enzyme paraoxonase 1 (PON1) is associated with high-density lipoprotein (HDL), and is responsible for many of HDLs' antiatherogenic properties. We previously showed that the flavonoid glabridin binds to rePON1 and affects the enzyme's 3D structure. This interaction protects the enzyme from inhibition by an atherogenic component of the human carotid plaque. Here, we broadened our study to an investigation of the structure-activity relationships (SARs) of 12 flavonoids from different subclasses with rePON1 using Trp-fluorescence quenching, modeling calculations and Cu(2+)-induced low-density lipoprotein (LDL) oxidation methods. Our findings emphasize the 'protein-binding' mechanism by which flavonoids exert their beneficial biological role toward rePON1. Flavonoids' capacity to interact with the enzyme's rePON1 hydrophobic groove mostly dictates their pro/antioxidant behavior.
DOI: 10.1016/j.bmc.2013.02.055
PubMed: 23623675
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000529
- to stream PubMed, to step Curation: 000527
- to stream PubMed, to step Checkpoint: 000507
- to stream Ncbi, to step Merge: 000573
- to stream Ncbi, to step Curation: 000573
- to stream Ncbi, to step Checkpoint: 000573
- to stream Main, to step Merge: 001054
- to stream Main, to step Curation: 001053
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The effects and mechanism of flavonoid-rePON1 interactions. Structure-activity relationship study.</title><author><name sortKey="Atrahimovich, Dana" sort="Atrahimovich, Dana" uniqKey="Atrahimovich D" first="Dana" last="Atrahimovich">Dana Atrahimovich</name><affiliation wicri:level="1"><nlm:affiliation>Oxidative Stress Research Laboratory, MIGAL-Galilee Research Institute, PO Box 831, Kiryat Shmona 11016, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>Oxidative Stress Research Laboratory, MIGAL-Galilee Research Institute, PO Box 831, Kiryat Shmona 11016</wicri:regionArea><wicri:noRegion>Kiryat Shmona 11016</wicri:noRegion></affiliation></author><author><name sortKey="Vaya, Jacob" sort="Vaya, Jacob" uniqKey="Vaya J" first="Jacob" last="Vaya">Jacob Vaya</name></author><author><name sortKey="Khatib, Soliman" sort="Khatib, Soliman" uniqKey="Khatib S" first="Soliman" last="Khatib">Soliman Khatib</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2013">2013</date><idno type="RBID">pubmed:23623675</idno><idno type="pmid">23623675</idno><idno type="doi">10.1016/j.bmc.2013.02.055</idno><idno type="wicri:Area/PubMed/Corpus">000529</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000529</idno><idno type="wicri:Area/PubMed/Curation">000527</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000527</idno><idno type="wicri:Area/PubMed/Checkpoint">000507</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000507</idno><idno type="wicri:Area/Ncbi/Merge">000573</idno><idno type="wicri:Area/Ncbi/Curation">000573</idno><idno type="wicri:Area/Ncbi/Checkpoint">000573</idno><idno type="wicri:Area/Main/Merge">001054</idno><idno type="wicri:Area/Main/Curation">001053</idno><idno type="wicri:Area/Main/Exploration">001053</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The effects and mechanism of flavonoid-rePON1 interactions. Structure-activity relationship study.</title><author><name sortKey="Atrahimovich, Dana" sort="Atrahimovich, Dana" uniqKey="Atrahimovich D" first="Dana" last="Atrahimovich">Dana Atrahimovich</name><affiliation wicri:level="1"><nlm:affiliation>Oxidative Stress Research Laboratory, MIGAL-Galilee Research Institute, PO Box 831, Kiryat Shmona 11016, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>Oxidative Stress Research Laboratory, MIGAL-Galilee Research Institute, PO Box 831, Kiryat Shmona 11016</wicri:regionArea><wicri:noRegion>Kiryat Shmona 11016</wicri:noRegion></affiliation></author><author><name sortKey="Vaya, Jacob" sort="Vaya, Jacob" uniqKey="Vaya J" first="Jacob" last="Vaya">Jacob Vaya</name></author><author><name sortKey="Khatib, Soliman" sort="Khatib, Soliman" uniqKey="Khatib S" first="Soliman" last="Khatib">Soliman Khatib</name></author></analytic><series><title level="j">Bioorganic & medicinal chemistry</title><idno type="eISSN">1464-3391</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Allosteric Site</term><term>Aryldialkylphosphatase (chemistry)</term><term>Copper (chemistry)</term><term>Flavonoids (chemistry)</term><term>Humans</term><term>Lipoproteins, HDL (chemistry)</term><term>Lipoproteins, LDL (chemistry)</term><term>Molecular Docking Simulation</term><term>Oxidation-Reduction</term><term>Protein Binding</term><term>Protein Conformation</term><term>Recombinant Proteins (chemistry)</term><term>Spectrometry, Fluorescence</term><term>Structure-Activity Relationship</term><term>Tryptophan (chemistry)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Aryldialkylphosphatase ()</term><term>Conformation des protéines</term><term>Cuivre ()</term><term>Flavonoïdes ()</term><term>Humains</term><term>Liaison aux protéines</term><term>Lipoprotéines HDL ()</term><term>Lipoprotéines LDL ()</term><term>Oxydoréduction</term><term>Protéines recombinantes ()</term><term>Relation structure-activité</term><term>Simulation de docking moléculaire</term><term>Site allostérique</term><term>Spectrométrie de fluorescence</term><term>Tryptophane ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Aryldialkylphosphatase</term><term>Copper</term><term>Flavonoids</term><term>Lipoproteins, HDL</term><term>Lipoproteins, LDL</term><term>Recombinant Proteins</term><term>Tryptophan</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Allosteric Site</term><term>Humans</term><term>Molecular Docking Simulation</term><term>Oxidation-Reduction</term><term>Protein Binding</term><term>Protein Conformation</term><term>Spectrometry, Fluorescence</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Aryldialkylphosphatase</term><term>Conformation des protéines</term><term>Cuivre</term><term>Flavonoïdes</term><term>Humains</term><term>Liaison aux protéines</term><term>Lipoprotéines HDL</term><term>Lipoprotéines LDL</term><term>Oxydoréduction</term><term>Protéines recombinantes</term><term>Relation structure-activité</term><term>Simulation de docking moléculaire</term><term>Site allostérique</term><term>Spectrométrie de fluorescence</term><term>Tryptophane</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Flavonoids are plant phenolic secondary metabolites that are widely distributed in the human diet. These antioxidants have received much attention because of their neuroprotective, cardioprotective, and chemopreventive actions. While a major focus has been on the flavonoids' antioxidant properties, there is an emerging view that many of the potential health benefits of flavonoids and their in vivo metabolites are due to modulatory actions in cells through direct interactions with proteins, and not necessarily due to their antioxidant function. This view relies on the observations that flavonoids are present in the circulation at very low concentrations, which are not sufficient to exert effective antioxidant effects. The enzyme paraoxonase 1 (PON1) is associated with high-density lipoprotein (HDL), and is responsible for many of HDLs' antiatherogenic properties. We previously showed that the flavonoid glabridin binds to rePON1 and affects the enzyme's 3D structure. This interaction protects the enzyme from inhibition by an atherogenic component of the human carotid plaque. Here, we broadened our study to an investigation of the structure-activity relationships (SARs) of 12 flavonoids from different subclasses with rePON1 using Trp-fluorescence quenching, modeling calculations and Cu(2+)-induced low-density lipoprotein (LDL) oxidation methods. Our findings emphasize the 'protein-binding' mechanism by which flavonoids exert their beneficial biological role toward rePON1. Flavonoids' capacity to interact with the enzyme's rePON1 hydrophobic groove mostly dictates their pro/antioxidant behavior.</div></front></TEI><affiliations><list><country><li>Israël</li></country></list><tree><noCountry><name sortKey="Khatib, Soliman" sort="Khatib, Soliman" uniqKey="Khatib S" first="Soliman" last="Khatib">Soliman Khatib</name><name sortKey="Vaya, Jacob" sort="Vaya, Jacob" uniqKey="Vaya J" first="Jacob" last="Vaya">Jacob Vaya</name></noCountry><country name="Israël"><noRegion><name sortKey="Atrahimovich, Dana" sort="Atrahimovich, Dana" uniqKey="Atrahimovich D" first="Dana" last="Atrahimovich">Dana Atrahimovich</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/StressCovidV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001053 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001053 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= StressCovidV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:23623675
|texte= The effects and mechanism of flavonoid-rePON1 interactions. Structure-activity relationship study.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:23623675" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a StressCovidV1
| This area was generated with Dilib version V0.6.33. |  |