Exploring benzoxaborole derivatives as carbonic anhydrase inhibitors: a structural and computational analysis reveals their conformational variability as a tool to increase enzyme selectivity.
Carbonic anhydrase inhibitors
X-ray crystallography
benzoxaborole derivatives
binding free energy calculations
structure-based drug design
Journal
Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
entrez:
20
8
2019
pubmed:
20
8
2019
medline:
3
10
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31423863
doi: 10.1080/14756366.2019.1653291
pmc: PMC6713116
doi:
Substances chimiques
Boron Compounds
0
Carbonic Anhydrase Inhibitors
0
Carbonic Anhydrases
EC 4.2.1.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1498-1505Références
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