Several structural motifs cooperate in determining the highly effective anti-thrombin activity of NU172 aptamer
| العنوان: | Several structural motifs cooperate in determining the highly effective anti-thrombin activity of NU172 aptamer |
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| المؤلفون: | Valeria Napolitano, Romualdo Troisi, I. Russo Krauss, V. A. Spiridonova, Filomena Sica |
| المساهمون: | Troisi, Romualdo, Napolitano, Valeria, Spiridonova, Vera, RUSSO KRAUSS, Irene, Sica, Filomena |
| المصدر: | 'Nucleic Acids Research ', vol: 46, pages: 12177-12185 (2018) Nucleic Acids Research |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Models, Molecular, 0301 basic medicine, Protein Conformation, Aptamer, Amino Acid Motifs, Oligonucleotides, Plasma protein binding, 030204 cardiovascular system & hematology, Biology, Crystallography, X-Ray, Ligands, G-quadruplex, 03 medical and health sciences, 0302 clinical medicine, Protein structure, Thrombin, Fibrinolytic Agents, Structural Biology, Hydrolase, Genetics, medicine, Humans, Structural motif, Circular Dichroism, Anticoagulants, Fibrinogen, Aptamers, Nucleotide, G-Quadruplexes, 030104 developmental biology, Duplex (building), Mutation, Biophysics, Protein Binding, medicine.drug |
| الوصف: | Despite aptamers are very promising alternative to antibodies, very few of them are under clinical trials or are used as drugs. Among them, NU172 is currently in Phase II as anticoagulant in heart disease treatments. It inhibits thrombin activity much more effectively than TBA, the best-known thrombin binding aptamer. The crystal structure of thrombin-NU172 complex reveals a bimodular duplex/quadruplex architecture for the aptamer, which binds thrombin exosite I through a highly complementary surface involving all three loops of the G-quadruplex module. Although the duplex domain does not interact directly with thrombin, the features of the duplex/quadruplex junction and the solution data on two newly designed NU172 mutants indicate that the duplex moiety is important for the optimization of the protein-ligand interaction and for the inhibition of the enzyme activity. Our work discloses the structural features determining the inhibition of thrombin by NU172 and put the basis for the design of mutants with improved properties. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0305-1048 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f8c3e57bb79b2ce1b21f355c0f7ab9d3Test https://epn-library.esrf.fr/flora/jsp/index_view_direct_anonymous.jsp?record=doc:PUB_ESRF:51073Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f8c3e57bb79b2ce1b21f355c0f7ab9d3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 03051048 |
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