Mapping the interaction site and effect of the Siglec-9 inflammatory biomarker on human primary amine oxidase
| Autor: | Leonor Lopes de Carvalho, Tiina A. Salminen, Gérard Vergoten, Gabriela Guédez, Jérôme de Ruyck, Sirpa Jalkanen, Heli Elovaara |
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| Přispěvatelé: | Åbo Akademi University [Turku], University of Turku, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), CNRS, Université de Lille, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], Université de Lille-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Amine oxidase AOC3 lcsh:Medicine Peptide Sialic acid binding Plasma protein binding Computational models Diagnostic markers Glycoproteins Inflammation peptides Article 03 medical and health sciences Humans Binding site lcsh:Science chemistry.chemical_classification Sialic Acid Binding Immunoglobulin-like Lectins Multidisciplinary Binding Sites 030102 biochemistry & molecular biology Chemistry lcsh:R SIGLEC respiratory system Ligand (biochemistry) Peptide Fragments Molecular Docking Simulation [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry 030104 developmental biology Biochemistry Mutation lcsh:Q Amine Oxidase (Copper-Containing) Cell Adhesion Molecules Protein Binding |
| Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2018, Scientific Reports, 8 (1), pp.2086. ⟨10.1038/s41598-018-20618-4⟩ Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) Scientific Reports, 2018, Scientific Reports, 8 (1), pp.2086. ⟨10.1038/s41598-018-20618-4⟩ |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-20618-4⟩ |
| Popis: | Human primary amine oxidase (hAOC3), also known as vascular adhesion protein 1, mediates leukocyte rolling and trafficking to sites of inflammation by a multistep adhesion cascade. hAOC3 is absent on the endothelium of normal tissues and is kept upregulated during inflammatory conditions, which is an applicable advantage for imaging inflammatory diseases. Sialic acid binding immunoglobulin like-lectin 9 (Siglec-9) is a leukocyte ligand for hAOC3. The peptide (CARLSLSWRGLTLCPSK) based on the region of Siglec-9 that interacts with hAOC3, can be used as a specific tracer for hAOC3-targeted imaging of inflammation using Positron Emission Tomography (PET). In the present study, we show that the Siglec-9 peptide binds to hAOC3 and triggers its amine oxidase activity towards benzylamine. Furthermore, the hAOC3 inhibitors semicarbazide and imidazole reduce the binding of wild type and Arg/Ala mutated Siglec-9 peptides to hAOC3. Molecular docking of the Siglec-9 peptide is in accordance with the experimental results and predicts that the R3 residue in the peptide interacts in the catalytic site of hAOC3 when the topaquinone cofactor is in the non-catalytic on-copper conformation. The predicted binding mode of Siglec-9 peptide to hAOC3 is supported by the PET studies using rodent, rabbit and pig AOC3 proteins. |
| Databáze: | OpenAIRE |
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