6h3q
Crystal structure of human carbonic anhydrase II in complex with the 4-(5-(chloromethyl)-1,3-selenazol-2-yl)benzenesulfonamide
Structural highlights
Disease[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.[1] [2] [3] [4] [5] Function[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.[6] [7] Publication Abstract from PubMedA series of disubstituted selenazole derivatives was synthetized and evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against the human (h) isoforms hCA I, II, IV, VA, VB and IX, involved in a variety of diseases including glaucoma, retinitis pigmentosa, epilepsy, arthritis and tumors. The investigated compounds showed potent inhibition against the tumor-associated transmembrane hCA IX, with KIs in the subnanomolar - low nanomolar range, and were evaluated for their effects on cell viability against the human prostate (PC3) and breast (MDA-MB-231) cancer cell lines, showing effective anti-tumor activity. These selenazoles are interesting leads for the development of new, isoform-selective CA IX inhibitors. Discovery of new 2, 5-disubstituted 1,3-selenazoles as selective human carbonic anhydrase IX inhibitors with potent anti-tumor activity.,Angeli A, Trallori E, Ferraroni M, Di Cesare Mannelli L, Ghelardini C, Supuran CT Eur J Med Chem. 2018 Sep 5;157:1214-1222. doi: 10.1016/j.ejmech.2018.08.096. Epub, 2018 Sep 3. PMID:30193219[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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