X-ray structure of alisporivir in complex with cyclophilin A at 1.5 Å resolution

Dujardin, Marie; Bouckaert, Julie; Rucktooa, Prakash; Hanoulle, Xavier

Type de document :

Article dans une revue scientifique

DOI :

10.1107/S2053230X18010415

URL permanente :

http://hdl.handle.net/20.500.12210/18734

Titre :

X-ray structure of alisporivir in complex with cyclophilin A at 1.5 Å resolution

Auteur(s) :

Dujardin, Marie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Bouckaert, Julie [Auteur]

Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Rucktooa, Prakash [Auteur]
Hanoulle, Xavier [Auteur]

Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Titre de la revue :

Acta crystallographica Section F : Structural biology communications [2014-...]

Numéro :

Pagination :

583-592

Date de publication :

2018-09

ISSN :

2053-230X

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

Alisporivir (ALV) is an 11-amino-acid hydrophobic cyclic peptide with N-methyl-D-alanine and N-ethyl-L-valine (NEV) residues at positions 3 and 4, respectively. ALV is a non-immunosuppressive cyclosporin A (CsA) derivative. ...
Lire la suite >Alisporivir (ALV) is an 11-amino-acid hydrophobic cyclic peptide with N-methyl-D-alanine and N-ethyl-L-valine (NEV) residues at positions 3 and 4, respectively. ALV is a non-immunosuppressive cyclosporin A (CsA) derivative. This inhibitor targets cyclophilins (Cyps), a family of proteins with peptidyl-prolyl cis/trans isomerase enzymatic activity. Cyps act as protein chaperones and are involved in numerous cellular functions. Moreover, Cyps have been shown to be an essential cofactor for the replication of many viruses, including Hepatitis C virus and Human immunodeficiency virus, and have also been shown to be involved in mitochondrial diseases. For these reasons, cyclophilins represent an attractive drug target. The structure of ALV in complex with cyclophilin A (CypA), the most abundant Cyp in humans, has been determined at 1.5 Å resolution. This first structure of the CypA–ALV complex shows that the binding of ALV is highly similar to that of CsA. The high resolution allowed the unambiguous determination of the conformations of residues 3 and 4 in ALV when bound to its target. In particular, the side-chain conformation of NEV4 precludes the interaction of the CypA–ALV complex with calcineurin, a cellular protein phosphatase involved in the immune response, which explains the non-immunosuppressive property of ALV. This study provides detailed molecular insights into the CypA–ALV interaction.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

CNRS
Université de Lille

Collections :

Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Computational Molecular Systems Biology

Date de dépôt :

2020-02-12T15:45:43Z
2024-02-19T08:59:01Z

Numéro de version	Lien	Date de modification
2	20.500.12210/18734*	2024-02-19T08:56:18Z
1	20.500.12210/18734.1	2020-02-12T15:45:43Z

X-ray structure of alisporivir in complex ...

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X-ray structure of alisporivir in complex ... BibTeX CSV Excel RIS

Historique des modifications

X-ray structure of alisporivir in complex ...

BibTeX

CSV

Excel

RIS