7NWY

Crystal structure of alpha carbonic anhydrase from schistosoma mansoni with 4-(3-(4-fluorophenyl)ureido)benzenesulfonamide

This is a non-PDB format compatible entry.

Summary for 7NWY

• Entry DOI: 10.2210/pdb7nwy/pdb
• Descriptor: Carbonic anhydrase, ZINC ION, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: schistosoma mansoni, carbonic anhydrase, metalloenzyme, inhibitor, neglected diseases, sulfonamide, lyase
• Biological source: Schistosoma mansoni (Blood fluke)
• Total number of polymer chains: 2
• Total formula weight: 73357.39

Authors

Angeli, A.,Ferraroni, M. (deposition date: 2021-03-17, release date: 2022-03-30, Last modification date: 2024-11-13)

Primary citation

Angeli, A.,Ferraroni, M.,Da'dara, A.A.,Selleri, S.,Pinteala, M.,Carta, F.,Skelly, P.J.,Supuran, C.T.
Structural Insights into Schistosoma mansoni Carbonic Anhydrase (SmCA) Inhibition by Selenoureido-Substituted Benzenesulfonamides.
J.Med.Chem., 64:10418-10428, 2021

PubMed Abstract: Tegumental carbonic anhydrase from the worm (SmCA) is considered a new anti-parasitic target because suppressing its expression interferes with schistosome metabolism and virulence. Here, we present the inhibition profiles of selenoureido compounds on recombinant SmCA and resolution of the first X-ray crystal structures of SmCA in adduct with a selection of such inhibitors. The key molecular features of such compounds in adduct with SmCA were obtained and compared to the human isoform hCA II, in order to understand the main structural factors responsible for enzymatic affinity and selectivity. Compounds that more specifically inhibited the schistosome versus human enzymes were identified. The results expand current knowledge in the field and pave the way for the development of more potent antiparasitic agents in the near future.

PubMed: 34232641
DOI: 10.1021/acs.jmedchem.1c00840

Experimental method

X-RAY DIFFRACTION (1.807 Å)