We have determined the protein X-ray crystal structures of four organometallic inhibitors in complex with their target enzyme carbonic anhydrase II. The barrel-shaped hydrophobic ferrocene and ruthenocene moieties have provided a structure-based avenue to better occupy the hydrophobic binding patch within the enzyme active site.

A soluble carbonic anhydrase (carbonate hydro-lyase, EC 4.2.1.1) has been purified to homogeneity from the membranous lateral wall (stria vascularis, spiral ligament, spiral prominence, and outer sulcus) of the guinea-pig inner ear. About 1% of the protein of the membranous lateral wall is carbonic anhydrase. The specific activity of the enzyme in homogenates of the lateral wall is 1.6-1.8 time...

Two molecular forms of carbonic anhydrase were identified in the rat anterior pituitary gland. Electrophoretic and immunological studies disclosed that the low activity carbonic anhydrase (type B) was associated with the particulate fraction of the pituitary gland and the high activity carbonic anhydrase (type C) was localized in the soluble fraction. The 800 times g pellet contained 50% of the...

Complexes of the diuretic benzothiadiazine derivative chlorothiazide (6-chloro-7-sulfamoyl- 1,2,4-benzothiadiazine-1,1-dioxide) with V(IV); Fe(II); Co(II); Ni(II); Cu(II), Ag(I) and U(VI) were prepared and characterized by elemental analysis, spectroscopic, thermogravimetric, magnetic and conductimetric measurements. The complexes behave as effective inhibitors for two isozymes (I and II) of ca...

A series of hydroxybenzoic acid derivatives have shown inhibitory activity against carbonic anhydrase (CA). X-ray crystallography shows that these molecules inhibit not by binding the active site metal ion but by strong hydrogen bonding to the metal-bound water nucleophile. The binding mode observed for these molecules is distinct when compared to other non-metal-binding CA inhibitors.

A shortage in the zinc supply to spinach (Spinacia oleracea L.) drastically reduced carbonic anhydrase levels with little effect on net CO(2) uptake per unit leaf area, except with the most severe zinc stresses. Under these conditions, carbonic anhydrase was below 10% and photosynthesis 60 to 70% of the control levels. When photosynthesis was measured at a range of CO(2) supply levels, zinc-def...

Carbonic anhydrase XII (CAXII) is a membrane enzyme that maintains pH homeostasis and sustains optimum P-glycoprotein (Pgp) efflux activity in cancer cells. Here, we investigated a panel of eight CAXII inhibitors (compounds 1-8), for their potential to reverse Pgp mediated tumor cell chemoresistance. Inhibitors (5 nM) were screened in human and murine cancer cells (colon, lung, breast, bone) wi...

Carbonic anhydrase IX (CA IX) is a surrogate marker of hypoxia, involved in survival and pH regulation in hypoxic cells. We have recently characterized its interactome, describing a set of proteins interacting with CA IX, mainly in hypoxic cells, including several members of the nucleocytoplasmic shuttling apparatuses. Accordingly, we described complex subcellular localization for this enzyme i...

CONTEXT A serum antibody to carbonic anhydrase II has been reported in patients with Sjögren's syndrome and idiopathic chronic pancreatitis. OBJECTIVE To evaluate cellular immune response to carbonic anhydrase II in patients with Sjögren's syndrome and idiopathic chronic pancreatitis. PATIENTS Idiopathic chronic pancreatitis (n=23), Sjögren's syndrome (n=12), alcoholic chronic pancreatitis ...

OBJECTIVES The relationship between adenosine deaminase and various cancers has been investigated in several studies. However, serum adenosine deaminase activity and carbonic anhydrase and catalase activities in patients with bladder cancer have not previously been reported. Therefore, the aim of this study was to measure serum adenosine deaminase, carbonic anhydrase and catalase activities in ...