Mapping the interaction site and effect ...
Document type :
Article dans une revue scientifique
PMID :
Permalink :
Title :
Mapping the interaction site and effect of the Siglec-9 inflammatory biomarker on human primary amine oxidase
Author(s) :
Lopes de Carvalho, Leonor [Auteur]
Åbo Akademi University [Turku]
Elovaara, Heli [Auteur]
University of Turku
De Ruyck, Jerome [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Vergoten, Gerard [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Jalkanen, Sirpa [Auteur]
University of Turku
Guédez, Gabriela [Auteur]
Åbo Akademi University [Turku]
Salminen, Tiina A. [Auteur]
Åbo Akademi University [Turku]
Åbo Akademi University [Turku]
Elovaara, Heli [Auteur]
University of Turku
De Ruyck, Jerome [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Vergoten, Gerard [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Jalkanen, Sirpa [Auteur]
University of Turku
Guédez, Gabriela [Auteur]
Åbo Akademi University [Turku]
Salminen, Tiina A. [Auteur]
Åbo Akademi University [Turku]
Journal title :
Scientific Reports
Abbreviated title :
Sci Rep
Volume number :
8
Pages :
2086
Publication date :
2018-02-01
ISSN :
2045-2322
English keyword(s) :
Computational models
Diagnostic markers
Glycoproteins
Inflammation
peptides
Diagnostic markers
Glycoproteins
Inflammation
peptides
HAL domain(s) :
Chimie/Chimie théorique et/ou physique
English abstract : [en]
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 ...
Show more >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.Show less >
Show more >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.Show less >
Language :
Anglais
Audience :
Non spécifiée
Administrative institution(s) :
CNRS
Université de Lille
Université de Lille
Research team(s) :
Diversité structurale des héparanes sulfates et régulation de la réponse inflammatoire
Computational Molecular Systems Biology
Computational Molecular Systems Biology
Submission date :
2020-02-12T15:11:24Z
2021-04-21T07:32:16Z
2021-04-21T07:32:16Z
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