Exploring the binding pocket for pyridopyrimidine ligands at the CCK1 receptor by molecular docking
Identifieur interne : 004392 ( Main/Exploration ); précédent : 004391; suivant : 004393Exploring the binding pocket for pyridopyrimidine ligands at the CCK1 receptor by molecular docking
Auteurs : Amel Toumi-Maouche [Algérie, France] ; Boubekeur Maouche [Algérie] ; Safia Taïri-Kellou [Algérie] ; Salima El-Aoufi [Algérie] ; Mercedes Martín-Martínez [Espagne] ; Rosario González-Mu Iz [Espagne] ; Daniel Fourmy [France] ; Bernard Maigret [France]Source :
- Journal of Molecular Modeling [ 1610-2940 ] ; 2008-04-01.
English descriptors
- KwdEn :
- mix :
Abstract
Abstract: Pyridopyrimidine-based analogues are among the most highly potent and selective antagonists of cholecystokinin receptor subtype-1 (CCK1R) described to date. To better understand the structural and chemical features responsible for the recognition mechanism, and to explore the binding pocket of these compounds, we performed automated molecular docking using GOLD2.2 software on some derivatives with structural diversity, and propose a putative binding conformation for each compound. The docking protocol was guided by the key role of the Asn333 residue, as revealed by site directed mutagenesis studies. The results suggest two putative binding modes located in the same pocket. Both are characterized by interaction with the main residues revealed by experiment, Asn333 and Arg336, and differ in the spatial position of the Boc-Trp moiety of these compounds. Hydrophobic contacts with residues Thr117, Phe107, Ile352 and Ile329 are also in agreement with experimental data. Despite the poor correlation obtained between the estimated binding energies and the experimental activity, the proposed models allow us to suggest a plausible explanation of the observed binding data in accordance with chemical characteristics of the compounds, and also to explain the observed diastereoselectivity of this family of antagonists towards CCK1R. The most reasonable selected binding conformations could be the starting point for future studies. Figure Superimposition of the two putative binding conformations revealed by molecular docking for pyridopyrimidine-based CCK1 antagonists
Url:
DOI: 10.1007/s00894-008-0271-6
Affiliations:
- Algérie, Espagne, France
- Communauté de Madrid, Grand Est, Lorraine (région), Midi-Pyrénées, Occitanie (région administrative), Wilaya d'Alger
- Alger, Madrid, Toulouse, Villers Les-Nancy
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 000426
- to stream Istex, to step Curation: 000423
- to stream Istex, to step Checkpoint: 000E20
- to stream Hal, to step Corpus: 002140
- to stream Hal, to step Curation: 002140
- to stream Hal, to step Checkpoint: 003645
- to stream Main, to step Merge: 004503
- to stream Main, to step Curation: 004392
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Exploring the binding pocket for pyridopyrimidine ligands at the CCK1 receptor by molecular docking</title><author><name sortKey="Toumi Maouche, Amel" sort="Toumi Maouche, Amel" uniqKey="Toumi Maouche A" first="Amel" last="Toumi-Maouche">Amel Toumi-Maouche</name></author><author><name sortKey="Maouche, Boubekeur" sort="Maouche, Boubekeur" uniqKey="Maouche B" first="Boubekeur" last="Maouche">Boubekeur Maouche</name></author><author><name sortKey="Tairi Kellou, Safia" sort="Tairi Kellou, Safia" uniqKey="Tairi Kellou S" first="Safia" last="Taïri-Kellou">Safia Taïri-Kellou</name></author><author><name sortKey="El Aoufi, Salima" sort="El Aoufi, Salima" uniqKey="El Aoufi S" first="Salima" last="El-Aoufi">Salima El-Aoufi</name></author><author><name sortKey="Martin Martinez, Mercedes" sort="Martin Martinez, Mercedes" uniqKey="Martin Martinez M" first="Mercedes" last="Martín-Martínez">Mercedes Martín-Martínez</name></author><author><name sortKey="Gonzalez Mu Iz, Rosario" sort="Gonzalez Mu Iz, Rosario" uniqKey="Gonzalez Mu Iz R" first="Rosario" last="González-Mu Iz">Rosario González-Mu Iz</name></author><author><name sortKey="Fourmy, Daniel" sort="Fourmy, Daniel" uniqKey="Fourmy D" first="Daniel" last="Fourmy">Daniel Fourmy</name></author><author><name sortKey="Maigret, Bernard" sort="Maigret, Bernard" uniqKey="Maigret B" first="Bernard" last="Maigret">Bernard Maigret</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:1363BE2253F500AFA35113F15168D1E79506B2C7</idno><date when="2008" year="2008">2008</date><idno type="doi">10.1007/s00894-008-0271-6</idno><idno type="url">https://api.istex.fr/ark:/67375/VQC-53Q8Z997-R/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000426</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000426</idno><idno type="wicri:Area/Istex/Curation">000423</idno><idno type="wicri:Area/Istex/Checkpoint">000E20</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000E20</idno><idno type="wicri:doubleKey">1610-2940:2008:Toumi Maouche A:exploring:the:binding</idno><idno type="wicri:source">HAL</idno><idno type="RBID">Hal:inria-00339125</idno><idno type="url">https://hal.inria.fr/inria-00339125</idno><idno type="wicri:Area/Hal/Corpus">002140</idno><idno type="wicri:Area/Hal/Curation">002140</idno><idno type="wicri:Area/Hal/Checkpoint">003645</idno><idno type="wicri:explorRef" wicri:stream="Hal" wicri:step="Checkpoint">003645</idno><idno type="wicri:doubleKey">0948-5023:2008:Toumi Maouche A:exploring:the:binding</idno><idno type="wicri:Area/Main/Merge">004503</idno><idno type="wicri:Area/Main/Curation">004392</idno><idno type="wicri:Area/Main/Exploration">004392</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Exploring the binding pocket for pyridopyrimidine ligands at the CCK1 receptor by molecular docking</title><author><name sortKey="Toumi Maouche, Amel" sort="Toumi Maouche, Amel" uniqKey="Toumi Maouche A" first="Amel" last="Toumi-Maouche">Amel Toumi-Maouche</name><affiliation wicri:level="3"><country xml:lang="fr">Algérie</country><wicri:regionArea>Laboratoire de Physico-Chimie Théorique et Chimie Informatique, Faculté de CHIMIE, USTHB B.P. 32, El Alia, Alger</wicri:regionArea><placeName><settlement type="city">Alger</settlement><region nuts="2">Wilaya d'Alger</region></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">France</country></affiliation></author><author><name sortKey="Maouche, Boubekeur" sort="Maouche, Boubekeur" uniqKey="Maouche B" first="Boubekeur" last="Maouche">Boubekeur Maouche</name><affiliation wicri:level="3"><country xml:lang="fr">Algérie</country><wicri:regionArea>Laboratoire de Physico-Chimie Théorique et Chimie Informatique, Faculté de CHIMIE, USTHB B.P. 32, El Alia, Alger</wicri:regionArea><placeName><settlement type="city">Alger</settlement><region nuts="2">Wilaya d'Alger</region></placeName></affiliation></author><author><name sortKey="Tairi Kellou, Safia" sort="Tairi Kellou, Safia" uniqKey="Tairi Kellou S" first="Safia" last="Taïri-Kellou">Safia Taïri-Kellou</name><affiliation wicri:level="3"><country xml:lang="fr">Algérie</country><wicri:regionArea>Laboratoire de Physico-Chimie Théorique et Chimie Informatique, Faculté de CHIMIE, USTHB B.P. 32, El Alia, Alger</wicri:regionArea><placeName><settlement type="city">Alger</settlement><region nuts="2">Wilaya d'Alger</region></placeName></affiliation></author><author><name sortKey="El Aoufi, Salima" sort="El Aoufi, Salima" uniqKey="El Aoufi S" first="Salima" last="El-Aoufi">Salima El-Aoufi</name><affiliation wicri:level="3"><country xml:lang="fr">Algérie</country><wicri:regionArea>Laboratoire de Physico-Chimie Théorique et Chimie Informatique, Faculté de CHIMIE, USTHB B.P. 32, El Alia, Alger</wicri:regionArea><placeName><settlement type="city">Alger</settlement><region nuts="2">Wilaya d'Alger</region></placeName></affiliation></author><author><name sortKey="Martin Martinez, Mercedes" sort="Martin Martinez, Mercedes" uniqKey="Martin Martinez M" first="Mercedes" last="Martín-Martínez">Mercedes Martín-Martínez</name><affiliation wicri:level="3"><country xml:lang="fr">Espagne</country><wicri:regionArea>Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006, Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Gonzalez Mu Iz, Rosario" sort="Gonzalez Mu Iz, Rosario" uniqKey="Gonzalez Mu Iz R" first="Rosario" last="González-Mu Iz">Rosario González-Mu Iz</name><affiliation wicri:level="3"><country xml:lang="fr">Espagne</country><wicri:regionArea>Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006, Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Fourmy, Daniel" sort="Fourmy, Daniel" uniqKey="Fourmy D" first="Daniel" last="Fourmy">Daniel Fourmy</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Equipe de Biologie et Pathologie Digestive, INSERM U531, Institut Louis Bugnard, CHU Rangueil, Bâtiment L3, 31403, Toulouse cedex 4</wicri:regionArea><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Maigret, Bernard" sort="Maigret, Bernard" uniqKey="Maigret B" first="Bernard" last="Maigret">Bernard Maigret</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire Lorrain de Recherche en Informatique et ses Applications, LORIA-615, Rue du Jardin Botanique, 54600, Villers Les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Villers Les-Nancy</settlement></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Molecular Modeling</title><title level="j" type="sub">Computational Chemistry - Life Sciences - Advanced Materials - New Methods</title><title level="j" type="abbrev">J Mol Model</title><idno type="ISSN">1610-2940</idno><idno type="eISSN">0948-5023</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Berlin/Heidelberg</pubPlace><date type="published" when="2008-04-01">2008-04-01</date><biblScope unit="volume">14</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="303">303</biblScope><biblScope unit="page" to="314">314</biblScope></imprint><idno type="ISSN">1610-2940</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1610-2940</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>CCK receptor antagonists</term><term>Cholecystokinin</term><term>Docking</term><term>Molecular modeling</term></keywords><keywords scheme="mix" xml:lang="en"><term>CCK receptor antagonists</term><term>Cholecystokinin</term><term>Docking</term><term>Molecular modeling</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Pyridopyrimidine-based analogues are among the most highly potent and selective antagonists of cholecystokinin receptor subtype-1 (CCK1R) described to date. To better understand the structural and chemical features responsible for the recognition mechanism, and to explore the binding pocket of these compounds, we performed automated molecular docking using GOLD2.2 software on some derivatives with structural diversity, and propose a putative binding conformation for each compound. The docking protocol was guided by the key role of the Asn333 residue, as revealed by site directed mutagenesis studies. The results suggest two putative binding modes located in the same pocket. Both are characterized by interaction with the main residues revealed by experiment, Asn333 and Arg336, and differ in the spatial position of the Boc-Trp moiety of these compounds. Hydrophobic contacts with residues Thr117, Phe107, Ile352 and Ile329 are also in agreement with experimental data. Despite the poor correlation obtained between the estimated binding energies and the experimental activity, the proposed models allow us to suggest a plausible explanation of the observed binding data in accordance with chemical characteristics of the compounds, and also to explain the observed diastereoselectivity of this family of antagonists towards CCK1R. The most reasonable selected binding conformations could be the starting point for future studies. Figure Superimposition of the two putative binding conformations revealed by molecular docking for pyridopyrimidine-based CCK1 antagonists</div></front></TEI><affiliations><list><country><li>Algérie</li><li>Espagne</li><li>France</li></country><region><li>Communauté de Madrid</li><li>Grand Est</li><li>Lorraine (région)</li><li>Midi-Pyrénées</li><li>Occitanie (région administrative)</li><li>Wilaya d'Alger</li></region><settlement><li>Alger</li><li>Madrid</li><li>Toulouse</li><li>Villers Les-Nancy</li></settlement></list><tree><country name="Algérie"><region name="Wilaya d'Alger"><name sortKey="Toumi Maouche, Amel" sort="Toumi Maouche, Amel" uniqKey="Toumi Maouche A" first="Amel" last="Toumi-Maouche">Amel Toumi-Maouche</name></region><name sortKey="El Aoufi, Salima" sort="El Aoufi, Salima" uniqKey="El Aoufi S" first="Salima" last="El-Aoufi">Salima El-Aoufi</name><name sortKey="Maouche, Boubekeur" sort="Maouche, Boubekeur" uniqKey="Maouche B" first="Boubekeur" last="Maouche">Boubekeur Maouche</name><name sortKey="Tairi Kellou, Safia" sort="Tairi Kellou, Safia" uniqKey="Tairi Kellou S" first="Safia" last="Taïri-Kellou">Safia Taïri-Kellou</name></country><country name="France"><noRegion><name sortKey="Toumi Maouche, Amel" sort="Toumi Maouche, Amel" uniqKey="Toumi Maouche A" first="Amel" last="Toumi-Maouche">Amel Toumi-Maouche</name></noRegion><name sortKey="Fourmy, Daniel" sort="Fourmy, Daniel" uniqKey="Fourmy D" first="Daniel" last="Fourmy">Daniel Fourmy</name><name sortKey="Maigret, Bernard" sort="Maigret, Bernard" uniqKey="Maigret B" first="Bernard" last="Maigret">Bernard Maigret</name></country><country name="Espagne"><region name="Communauté de Madrid"><name sortKey="Martin Martinez, Mercedes" sort="Martin Martinez, Mercedes" uniqKey="Martin Martinez M" first="Mercedes" last="Martín-Martínez">Mercedes Martín-Martínez</name></region><name sortKey="Gonzalez Mu Iz, Rosario" sort="Gonzalez Mu Iz, Rosario" uniqKey="Gonzalez Mu Iz R" first="Rosario" last="González-Mu Iz">Rosario González-Mu Iz</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Lorraine/explor/InforLorV4/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 004392 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 004392 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Lorraine
|area= InforLorV4
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:1363BE2253F500AFA35113F15168D1E79506B2C7
|texte= Exploring the binding pocket for pyridopyrimidine ligands at the CCK1 receptor by molecular docking
}}
| This area was generated with Dilib version V0.6.33. |  |