Inhibition studies of a beta-carbonic anhydrase from Brucella suis with a series of water soluble glycosyl sulfanilamides.

Article Details

Citation

Copy to clipboard

Vullo D, Nishimori I, Scozzafava A, Kohler S, Winum JY, Supuran CT

Inhibition studies of a beta-carbonic anhydrase from Brucella suis with a series of water soluble glycosyl sulfanilamides.

Bioorg Med Chem Lett. 2010 Apr 1;20(7):2178-82. doi: 10.1016/j.bmcl.2010.02.042. Epub 2010 Feb 21.

PubMed ID

20211561 [ View in PubMed

]

Abstract

A beta-carbonic anhydrase (CA, EC 4.2.1.1) from the bacterial pathogen Brucella suis, bsCA 1, has been cloned, purified characterized kinetically and for inhibition with a series of water soluble glycosylated sulfanilamides. bsCA 1 has appreciable activity as catalyst for the hydration of CO(2) to bicarbonate, with a k(cat) of 6.4x10(5) s(-1) and k(cat)/K(m) of 3.9x10(7) M(-1) s(-1). All types of inhibitory activities have been detected, with K(I)s in the range of 8.9-110 nM. The best bsCA 1 inhibitor were the galactose and ribose sulfanilamides, with inhibition constants of 8.9-9.2 nM. Small structural changes in the sugar moiety led to dramatic differences of enzyme inhibitory activity for this series of compounds. One of the tested glycosylsulfonamides and acetazolamide significantly inhibited the growth of the bacteria in cell cultures.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Acetazolamide	Carbonic anhydrase 1	Ki (nM)	250	N/A	N/A	Details
Acetazolamide	Carbonic anhydrase 2	Ki (nM)	12	N/A	N/A	Details