8fr2
Carbonic Anhydrase IX-mimic in complex with the alkyl urea compound 3h
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 PubMedThis paper reports an investigation into the impact of pyridyl functional groups in conjunction with hydroxide-substituted benzenesulfonamides on the inhibition of human carbonic anhydrase (CA; EC 4.2.1.1) enzymes. These compounds were tested in vitro of CA II and CA IX, two physiologically important CA isoforms. The most potent inhibitory molecules against CA IX, 3g, 3h, and 3k, were studied to understand their binding modes via X-ray crystallography in adduct with CA II and CA IX-mimic. This research further adds to the field of CA inhibitors to better understand ligand selectivity between isoforms found in humans. New Insights into Conformationally Restricted Carbonic Anhydrase Inhibitors.,Combs J, Bozdag M, Cravey LD, Kota A, McKenna R, Angeli A, Carta F, Supuran CT Molecules. 2023 Jan 16;28(2):890. doi: 10.3390/molecules28020890. PMID:36677947[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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