Exploring benzoxaborole derivatives as carbonic anhydrase inhibitors: a structural and computational analysis reveals their conformational variability as a tool to increase enzyme selectivity
Exploring benzoxaborole derivatives as carbonic anhydrase inhibitors: a structural and computational analysis reveals their conformational variability as a tool to increase enzyme selectivity(385 views) Langella E, Alterio V, D'Ambrosio K, Cadoni R, Winum JY, Supuran CT, Monti SM, De Simone G, Di Fiore A
Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche , Naples , Italy., Institut des Biomolecules Max Mousseron (IBMM) UMR 5247 CNRS, ENSCM, Universite de Montpellier, Ecole Nationale Superieure de Chimie de Montpellier , Montpellier , France., Dipartimento di Chimica e Farmacia, Universita Degli Studi di Sassari , Sassari , Italy., Neurofarba Department, Section of Pharmaceutical and Nutriceutical Sciences, Universita Degli Studi di Firenze , Florence , Italy.,
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Exploring benzoxaborole derivatives as carbonic anhydrase inhibitors: a structural and computational analysis reveals their conformational variability as a tool to increase enzyme selectivity
Recent studies identified the benzoxaborole moiety as a new zinc-binding group able to interact with carbonic anhydrase (CA) active site. Here, we report a structural analysis of benzoxaboroles containing urea/thiourea groups, showing that these molecules are very versatile since they can bind the enzyme assuming different binding conformations and coordination geometries of the catalytic zinc ion. In addition, theoretical calculations of binding free energy were performed highlighting the key role of specific residues for protein-inhibitor recognition. Overall, these data are very useful for the development of new inhibitors with higher selectivity and efficacy for various CAs.
Exploring benzoxaborole derivatives as carbonic anhydrase inhibitors: a structural and computational analysis reveals their conformational variability as a tool to increase enzyme selectivity
Exploring benzoxaborole derivatives as carbonic anhydrase inhibitors: a structural and computational analysis reveals their conformational variability as a tool to increase enzyme selectivity