5FDC

Crystal structure of Human Carbonic Anhydrase II in complex with the anticonvulsant sulfamide JNJ-26990990 and its S,S-dioxide analog.

Summary for 5FDC

• Entry DOI: 10.2210/pdb5fdc/pdb
• Related: 1CA2
• Descriptor: Carbonic anhydrase 2, ZINC ION, 3-[(sulfamoylamino)methyl]-1-benzothiophene, ... (6 entities in total)
• Functional Keywords: sulfamide inhibitor, protein-inhibitor complex, lyase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : P00918
• Total number of polymer chains: 1
• Total formula weight: 30027.59

Authors

Di Fiore, A.,De Simone, G.,Alterio, V.,Riccio, V.,Winum, J.-Y.,Carta, F.,Supuran, C.T. (deposition date: 2015-12-16, release date: 2016-05-18, Last modification date: 2024-01-10)

Primary citation

Di Fiore, A.,De Simone, G.,Alterio, V.,Riccio, V.,Winum, J.Y.,Carta, F.,Supuran, C.T.
The anticonvulsant sulfamide JNJ-26990990 and its S,S-dioxide analog strongly inhibit carbonic anhydrases: solution and X-ray crystallographic studies.
Org.Biomol.Chem., 14:4853-4858, 2016

PubMed Abstract: JNJ-26990990 ((benzo[b]thien-3-yl)methyl)sulfamide, a sulfamide derivative structurally related to the antiepileptic drug zonisamide, was reported to be devoid of carbonic anhydrase (CA, EC 4.2.1.1) inhibitory properties. Here we report that JNJ-26990990 and its S,S-dioxide analog significantly inhibit six human (h) isoforms, hCA I, II, VII, IX, XII and XIV, involved in crucial physiological processes. Inhibition and X-ray crystallographic data for the binding of the two compounds to these enzymes show significant similarity with the zonisamide inhibitory pattern. These findings prompted us to reconsider the structural/pharmacological requirements for designing effective antiepileptics possessing zinc-binding groups of the sulfamide, sulfamate or sulfonamide type in their molecules.

PubMed: 27151329
DOI: 10.1039/c6ob00803h

Experimental method

X-RAY DIFFRACTION (1.75 Å)