Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Journal of Enzyme Inhibition and Medicinal Chemistry Année : 2017

Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations

Résumé

Sulphamate and sulphamide derivatives have been largely investigated as carbonic anhydrase inhibitors (CAIs) by means of different experimental techniques. However, the structural determinants responsible for their different binding mode to the enzyme active site were not clearly defined so far. In this paper, we report the X-ray crystal structure of hCA II in complex with a sulphamate inhibitor incorporating a nitroimidazole moiety. The comparison with the structure of hCA II in complex with its sulphamide analogue revealed that the two inhibitors adopt a completely different binding mode within the hCA II active site. Starting from these results, we performed a theoretical study on sulphamate and sulphamide derivatives, demonstrating that electrostatic interactions with residues within the enzyme active site play a key role in determining their binding conformation. These findings open new perspectives in the design of effective CAIs using the sulphamate and sulphamide zinc binding groups as lead compounds.

Domaines

Chimie
Fichier principal
Vignette du fichier
Insights into the binding mode of sulphamates and sulphamides to hCA II crystallographic studies and binding free energy calculations.pdf (3.28 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03621657 , version 1 (28-03-2022)

Licence

Paternité

Identifiants

Citer

Giuseppina de Simone, Emma Langella, Davide Esposito, Claudiu Supuran, Simona Maria Monti, et al.. Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations. Journal of Enzyme Inhibition and Medicinal Chemistry, 2017, 32 (1), pp.1002-1011. ⟨10.1080/14756366.2017.1349764⟩. ⟨hal-03621657⟩
8 Consultations
18 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More