A Combined Crystallographic and Theoretical Study Explains the Capability of Carboxylic Acids to Adopt Multiple Binding Modes in the Active Site of Carbonic Anhydrases.
Carboxylates are the least investigated class of inhibitors of carbonic anhydrases (CAs). Here we explain the versatility of binding of these molecules to CAs by examining a new adduct of hCA II with N-carboxymethyl-saccharin.
Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Napoli (Italy).
Emma
E
Langella
Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Napoli (Italy). katia.dambrosio@cnr.it.
Katia
K
D'Ambrosio
Target Discovery Institute, University of Oxford, NDM Research Building, Roosevelt Drive, Headington, Oxford OX3 7FZ (UK).
Melissa
M
D'Ascenzio
Department of Pharmacy, "G. D'Annunzio" University of Chieti, Via dei Vestini 31, 66100 Chieti (Italy).
Simone
S
Carradori
Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Napoli (Italy).
Simona M
SM
Monti
Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence (Italy).|NEUROFARBA Department, Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence (Italy).
Claudiu T
CT
Supuran
Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Napoli (Italy). gdesimon@unina.it.
Giuseppina
G
De Simone
D001665:Binding Sites; D024402:Carbonic Anhydrase II / Q000737:chemistry*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry*; D002256:Carbonic Anhydrases / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D012439:Saccharin / Q000031:analogs & derivatives* / Q000737:chemistry; D013449:Sulfonamides / Q000737:chemistry*
D002257:Carbonic Anhydrase Inhibitors; D002264:Carboxylic Acids; C000608456:N-carboxymethyl-saccharin; D013449:Sulfonamides; D024402:Carbonic Anhydrase II; D002256:Carbonic Anhydrases; D012439:Saccharin
X-ray structures; carbonic anhydrases; drug design; inhibitors; theoretical calculations