Carbonic anhydrase inhibitors. X-ray crystal studies of the carbonic anhydrase II-trithiocarbonate adduct--an inhibitor mimicking the sulfonamide and urea binding to the enzyme.

Article Details

Citation

Copy to clipboard

Temperini C, Scozzafava A, Supuran CT

Carbonic anhydrase inhibitors. X-ray crystal studies of the carbonic anhydrase II-trithiocarbonate adduct--an inhibitor mimicking the sulfonamide and urea binding to the enzyme.

Bioorg Med Chem Lett. 2010 Jan 15;20(2):474-8. doi: 10.1016/j.bmcl.2009.11.124. Epub 2009 Nov 27.

PubMed ID

20005709 [ View in PubMed

]

Abstract

Trithiocarbonate (CS32-) inhibits with low micromolar affinities several mammalian carbonic anhydrases, CAs, EC 4.2.1.1 [Innocenti et al., Bioorg. Med. Chem. Lett. 2009, 19, 1855]. Here we report the X-ray crystal structure of the hCA II-trithiocarbonate adduct. Trithiocarbonate is monodentately bound to the Zn(II) ion and makes several hydrogen bonds with Thr199 and two water molecules from the enzyme active site. Its binding is different from that of ureate, another small inhibitor isosteric with trithiocarbonate but somehow mimicks the binding of the SO(2)NH moiety present in the sulfonamide inhibitors and is similar to that of bicarbonate. Compounds incorporating this new zinc-binding group, CS2-, may thus lead to new classes of potent inhibitors.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Urea	Carbonic anhydrase 2	Protein	Humans	Unknown	Not Available	Details