Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations(189 views visite) De Simone G, Langella E, Esposito D, Supuran CT, Monti SM, Winum JY, Alterio V
Keywords Parole chiave: Carbonic Anhydrase, Binding Free Energy Calculations, Crystal Structure,
Affiliations Affiliazioni: *** IBB - CNR ***
a Istituto di Biostrutture e Bioimagini , Consiglio Nazionale delle Ricerche , Naples , Italy., b Neurofarba Department, Section of Pharmaceutical and Nutriceutical Sciences , Universita degli Studi di Firenze , Sesto Fiorentino , Florence , Italy., c Institut des Biomolecules Max Mousseron, UMR 5247 CNRS, ENSCM , Universite de Montpellier , Montpellier , France.,
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Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations
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.
Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations
268 Records (263 escludendo Abstract e Conferenze). Impact factor totale: 1146.583 (1127.535 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 1091.314 (1070.968 escludendo Abstract e Conferenze).
Last modified by Ultima modifica di Gennaro Angrisano on in data Sunday 12 July 2020, 13:14:42 189 views visite. Last view on Ultima visita in data Saturday 23 January 2021, 1:48:20