Evidence for subdomain flexibility in Drosophila melanogaster acetylcholinesterase
| العنوان: | Evidence for subdomain flexibility in Drosophila melanogaster acetylcholinesterase |
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| المؤلفون: | Jure Stojan, Omid Ranei Siadat, Didier Fournier, Laurent Paquereau, Caroline Ladurantie |
| المساهمون: | Medical Faculty, Institute of Biochemistry, University of Ljubljana, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées |
| المصدر: | Biochemistry Biochemistry, American Chemical Society, 2008, 47 (20), pp.5599-607. ⟨10.1021/bi7025479⟩ |
| بيانات النشر: | HAL CCSD, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Models, Molecular, Hydrodynamic radius, Flexibility (anatomy), MESH: Mutation, Stereochemistry, Biochemistry, Substrate Specificity, MESH: Drosophila melanogaster, 03 medical and health sciences, chemistry.chemical_compound, MESH: Protein Structure, Tertiary, medicine, Animals, MESH: Animals, MESH: Disulfides, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Disulfides, Mutated protein, 030304 developmental biology, 0303 health sciences, biology, MESH: Kinetics, Chemistry, Hydrolysis, 030302 biochemistry & molecular biology, Active site, MESH: Chromatography, Gel, MESH: Acetylcholinesterase, biology.organism_classification, Acetylcholinesterase, Protein Structure, Tertiary, Folding (chemistry), Kinetics, medicine.anatomical_structure, Drosophila melanogaster, Mutation, biology.protein, Chromatography, Gel, Phosphorylation, MESH: Substrate Specificity, MESH: Hydrolysis, MESH: Models, Molecular |
| الوصف: | International audience; The catalytic domain of the acetylcholinesterases is composed of a single polypeptide chain, the folding of which determines two subdomains. We have linked these two subdomains by mutating two residues, I327 and D375, to cysteines, to form a disulfide bridge. As a consequence, the hydrodynamic radius of the protein was reduced, suggesting that there is some flexibility in the subdomain connection. In addition to the smaller size, the mutated protein is more stable than the wild-type protein. Therefore, the flexibility between the two domains is a weak point in terms of protein stability. As expected from the location of the disulfide bond at the rim of the active site, the kinetic studies show that it affects interactions with peripheral ligands and the entrance of some of the bulkier substrates, like o-nitrophenyl acetate. In addition, the mutations affect the catalytic step for o-nitrophenyl acetate and phosphorylation by organophosphates, suggesting that this movement between the two subdomains is connected with the cooperativity between the peripheral and catalytic sites. |
| اللغة: | English |
| تدمد: | 0006-2960 1520-4995 |
| DOI: | 10.1021/bi7025479⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7692ca26d6a4eb0f68d6acd9d9b0938d https://hal.archives-ouvertes.fr/hal-00374673 |
| رقم الانضمام: | edsair.doi.dedup.....7692ca26d6a4eb0f68d6acd9d9b0938d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00062960 15204995 |
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| DOI: | 10.1021/bi7025479⟩ |