Carbonic anhydrase IX mimic in complex with (E)-2-(5-bromo-2- hydroxyphenyl)ethenesulfonic acid
[CAH2_HUMAN] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:259730]; also known as osteopetrosis with renal tubular acidosis, carbonic anhydrase II deficiency syndrome, Guibaud-Vainsel syndrome or marble brain disease. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.    
[CAH2_HUMAN] Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. 
Publication Abstract from PubMed
Coumarins were recently shown to constitute a novel class of mechanism-based carbonic anhydrase (CA, EC 126.96.36.199) inhibitors. We demonstrate that sulfocoumarins (1,2-benzoxathiine 2,2-dioxides) possess a similar mechanism of action, acting as effective CA inhibitors. The sulfocoumarins were hydrolyzed by the esterase CA activity to 2-hydroxyphenyl-vinylsulfonic acids, which thereafter bind to the enzyme in a region rarely occupied by other classes of inhibitors. The X-ray structure of one of these compounds in adduct with a modified CA II enzyme possessing two amino acid residues from the CA IX active site, allowed us to decipher the inhibition mechanism. The sulfonic acid was observed anchored to the zinc-coordinated water molecule, making favorable interactions with Thr200 and Pro201. Some other sulfocoumarins incorporating substituted-1,2,3-triazole moieties were prepared by using click chemistry and showed low nanomolar inhibitory action against the tumor-associated isoforms CA IX and XII, being less effective against the cytosolic CA I and II.
Sulfocoumarins (1,2-Benzoxathiine-2,2-dioxides): A Class of Potent and Isoform-Selective Inhibitors of Tumor-Associated Carbonic Anhydrases.,Tars K, Vullo D, Kazaks A, Leitans J, Lends A, Grandane A, Zalubovskis R, Scozzafava A, Supuran CT J Med Chem. 2013 Jan 10;56(1):293-300. doi: 10.1021/jm301625s. Epub 2012 Dec 27. PMID:23241068
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.