Out of the active site binding pocket for carbonic anhydrase inhibitors

Abstract

A structural study of the adduct which 2-benzylsulfinylbenzoic acid forms with human carbonic anhydrase II is reported, showing a binding mode completely different from any other class of carbonic anhydrase inhibitors investigated so far; this carboxylate binds in a pocket situated out of the enzyme active site.

Prosystemin, a prohormone that modulates plant defense barriers, is an intrinsically disordered protein

“…Proteolysis was monitored by SDS‐PAGE upon a digestion time of 30 min, 1 h, 2 h, 16 h at 26°C. Carbonic anhydrase II (homemade) was used as a control.…”

Cloning, characterization and anion inhibition studies of a γ-carbonic anhydrase from the Antarctic cyanobacterium Nostoc commune

“…49.2 nt 0.090 0.084 § As sodium salt; nt = not tested. # Errors were in the range of 3-5% of the reported values, from three different assays.…”

“…10,[14][15][16] Most data reported in literature are referred to CAs isolated from mesophilic sources (mammals or prokaryotes) with an optimum temperature range of around 37°C. [48][49][50][51][52][53][54][55][56][57][58][59][60] Recently we started to investigate CAs from microorganisms living in extreme environments, such as extremophiles from volcanic environments which are able to survive at temperatures as high as 110°C in harsh environments in which high concentrations of CO 2 , H 2 S or other gases are present. 24,26,28,29,31,43,61,62 In this context, we thought it might be of interest to start the study of CAs from microorganisms living in extremely cold habitats, such as the Antarctic continent.…”

Inhibition of carbonic anhydrase IX targets primary tumors, metastases, and cancer stem cells: Three for the price of one

“…This first nonsulfonamide CA IX inhibition study showed that acetate, lactate, and benzoate were highly ineffective inhibitors, whereas 2,3,5,6‐ tetrafluororobenzoate ( 14 ) (Figure ) was a more effective hCA IX inhibitor with a K I of 0.77 mM . Subsequent studies evidenced that carboxylates of types 15–18 possess much better hCA IX inhibitory properties compared to 14 , usually in the micromolar range. Moreover, X‐ray crystallography (mainly using CA II as CA IX model) showed a wide range of inhibition mechanisms, as some of these carboxylates coordinate (monodentately) to the zinc ion, others anchor to the zinc‐coordinated water molecule, others occlude the entrance to the active site (see Section ), whereas 18 binds out of the active site .…”