7NC4

Crystal structure of human carbonic anhydrase VII (hCA VII) in complex with a 4-(4-aroylpiperazine-1-carbonyl)benzenesulfonamide derivative.

Summary for 7NC4

• Entry DOI: 10.2210/pdb7nc4/pdb
• Descriptor: Carbonic anhydrase 7, ZINC ION, 4-[4-(2-chlorophenyl)carbonylpiperazin-1-yl]carbonylbenzenesulfonamide, ... (5 entities in total)
• Functional Keywords: protein-inhibitor adduct, lyase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 31583.16

Authors

Di Fiore, A.,De Simone, G. (deposition date: 2021-01-28, release date: 2021-07-14, Last modification date: 2024-11-13)

Primary citation

Mancuso, F.,Di Fiore, A.,De Luca, L.,Angeli, A.,De Simone, G.,Supuran, C.T.,Gitto, R.
Design, synthesis and biochemical evaluation of novel carbonic anhydrase inhibitors triggered by structural knowledge on hCA VII.
Bioorg.Med.Chem., 44:116279-116279, 2021

PubMed Abstract: To tackle the challenge of isoform selectivity, we explored the entrance of the cavity for selected druggable human Carbonic Anhydrases (hCAs). Based on X-ray crystallographic studies on the 4-(4-(2-chlorobenzoyl)piperazine-1-carbonyl)benzenesulfonamide in complex with the brain expressed hCA VII (PDB code: 7NC4), a series of 4-(4(hetero)aroylpiperazine-1-carbonyl)benzene-1-sulfonamides has been developed. To evaluate their capability to fit the hCA VII catalytic cavity, the newer benzenesulfonamides were preliminary investigated by means of docking simulations. Then, this series of thirteen benzenesulfonamides was synthesized and tested against selected druggable hCAs. Among them, the 4-(4-(furan-2-carbonyl)piperazine-1-carbonyl)benzenesulfonamide showed remarkable affinity towards hCA VII (K: 4.3 nM) and good selectivity over the physiologically widespread hCA I when compared to Topiramate (TPM).

PubMed: 34216985
DOI: 10.1016/j.bmc.2021.116279

Experimental method

X-RAY DIFFRACTION (1.6 Å)