3caj

Crystal structure of the human carbonic anhydrase II in complex with ethoxzolamide

spinqualitylabelsall models 3caj, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3caj is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, EZL, GOL, MBO, ZN Related: 1ca2, 1cil, 1a42 Activity: Carbonate dehydratase, with EC number 4.2.1.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Ethoxzolamide, an almost forgotten inhibitor of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), is the only classical inhibitor whose structure in adduct with any isoform was not reported yet. We report here the inhibition data of this molecule with the 12 catalytically active mammalian isozymes (CA I-CA XIV) and the X-ray crystal structure with the cytosolic, ubiquitous isoform CA II. These data are presumably useful for the design of novel CA inhibitors, targeting various CA isozymes, considering that ethoxzolamide was already the lead molecule to obtain the second generation inhibitors, dorzolamide and brinzolamide, clinically used antiglaucoma agents with topical action, as well as various other investigational agents. Carbonic anhydrase inhibitors: the X-ray crystal structure of ethoxzolamide complexed to human isoform II reveals the importance of thr200 and gln92 for obtaining tight-binding inhibitors.,Di Fiore A, Pedone C, Antel J, Waldeck H, Witte A, Wurl M, Scozzafava A, Supuran CT, De Simone G Bioorg Med Chem Lett. 2008 Apr 15;18(8):2669-74. Epub 2008 Mar 18. PMID:18359629 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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