8C0Q

Crystal structure of human carbonic anhydrase II in complex with a coumarin derivative.

Summary for 8C0Q

• Entry DOI: 10.2210/pdb8c0q/pdb
• Descriptor: Carbonic anhydrase 2, ZINC ION, (4-methyl-2-oxidanylidene-chromen-7-yl)methanesulfonamide, ... (4 entities in total)
• Functional Keywords: methylsuolfonamide, protein-inhibitor complex, carbonic anhydrase ii, coumarin, lyase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 29664.79

Authors

Alterio, V.,De Simone, G.,Esposito, D. (deposition date: 2022-12-19, release date: 2023-03-08, Last modification date: 2024-02-14)

Primary citation

Langella, E.,Esposito, D.,Monti, S.M.,Supuran, C.T.,De Simone, G.,Alterio, V.
A Combined in Silico and Structural Study Opens New Perspectives on Aliphatic Sulfonamides, a Still Poorly Investigated Class of CA Inhibitors.
Biology (Basel), 12:-, 2023

PubMed Abstract: Aliphatic sulfonamides are an interesting class of carbonic anhydrase inhibitors (CAIs) proven to be effective for several carbonic anhydrase (CA) isoforms involved in pathologic states. Here we report the crystallographic structures of hCA II in complex with two aliphatic sulfonamides incorporating coumarin rings, which showed a good inhibition and selectivity for this isoform. Although these two molecules have a very similar chemical structure, differing only in the substitution of the two aliphatic hydrogen atoms with two fluorine atoms, they adopt a significantly different binding mode within the enzyme active site. Theoretical binding free energy calculations, performed to rationalize these data, showed that a delicate balance of electrostatic and steric effects modulate the protein-ligand interactions. Data presented here can be fruitfully used for the rational design of novel and effective isozyme-specific inhibitor molecules.

PubMed: 36829558
DOI: 10.3390/biology12020281

Experimental method

X-RAY DIFFRACTION (1.67 Å)