PDBsum entry 5fdc

Lyase

PDB id: 5fdc

Contents

Protein chain

258 a.a.

Ligands

5WN

GOL

HGB

Metals

_ZN

Waters ×264

References listed in PDB file

Key reference

• Title: The anticonvulsant sulfamide jnj-26990990 and its s,S-Dioxide analog strongly inhibit carbonic anhydrases: solution and x-Ray crystallographic studies.
• Authors: A.Di fiore, G.De simone, V.Alterio, V.Riccio, J.Y.Winum, F.Carta, C.T.Supuran.
• Ref.: Org Biomol Chem, 2016, 14, 4853-4858. [DOI no: 10.1039/c6ob00803h]
• PubMed id: 27151329

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.