7asj
Crystal structure for the complex of human carbonic anhydrase II and 3-(3-methyl-3-phenethylureido)benzenesulfonamide
Structural highlights
DiseaseCAH2_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] FunctionCAH2_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 PubMedWe report a one-pot procedure for the synthesis of asymmetrical ureido-containing benzenesulfonamides based on in situ generation of the corresponding isocyanatobenezenesulfonamide species, which were trapped with the appropriate amines. A library of new compounds was generated and evaluated in vitro for their inhibition properties against a representative panel of the human (h) metalloenzymes carbonic anhydrases (EC 4.2.1.1), and the best performing compounds on the isozyme II (i.e., 7c, 9c, 11g, and 12c) were screened for their ability to reduce the intraocular pressure in glaucomatous rabbits. In addition, the binding modes of 7c, 11f, and 11g were assessed by means of X-ray crystallography. One-Pot Procedure for the Synthesis of Asymmetric Substituted Ureido Benzene Sulfonamides as Effective Inhibitors of Carbonic Anhydrase Enzymes.,Vannozzi G, Vullo D, Angeli A, Ferraroni M, Combs J, Lomelino C, Andring J, Mckenna R, Bartolucci G, Pallecchi M, Lucarini L, Sgambellone S, Masini E, Carta F, Supuran CT J Med Chem. 2022 Jan 13;65(1):824-837. doi: 10.1021/acs.jmedchem.1c01906. Epub, 2021 Dec 27. PMID:34958217[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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