6h33

The crystal structure of human carbonic anhydrase II in complex with 4-(4-phenyl)-4-hydroxy-1-piperidine-1-carbonyl)benzenesulfonamide.The crystal structure of human carbonic anhydrase II in complex with 4-(4-phenyl)-4-hydroxy-1-piperidine-1-carbonyl)benzenesulfonamide.

Structural highlights 6h33 is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , Related: 6h2z 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. Publication Abstract from PubMed Guided by the crystal structure of 4-(3,4-dihydroquinolin-1(2H)-ylcarbonyl)benzenesulfonamide 3 in complex with hCA II (PDB code 4Z0Q), a novel series of cycloalkylamino-1-carbonylbenzenesulfonamides was designed and synthesized. Thus, we replaced the quinoline ring with an azepine/piperidine/piperazine nucleus and introduced further modifications on cycloalkylamine nucleus by means the installation of hydrophobic/hydrophilic functionalities able to establish additional contacts in the middle area of the enzyme cavity. Among the synthesized compounds, the derivatives 7a, 7b, 8b exhibited a remarkable inhibition for hCA II and the brain-expressed hCA VII in subnanomolar range. The binding of these molecules to the target enzymes was characterized by means of a crystallographic analysis, providing a clear snapshot of the most important interactions established by this class of inhibitors into the hCA II and hCA VII catalytic site. Notably, our results showed that the benzylpiperazine tail of compound 8b is oriented both in hCA II and in hCA VII toward a poorly explored region of the active site. These features should be further investigated for the design of new isoform selective CA inhibitors. Exploring structural properties of potent human carbonic anhydrase inhibitors bearing a 4-(cycloalkylamino-1-carbonyl)benzenesulfonamide moiety.,Buemi MR, Di Fiore A, De Luca L, Angeli A, Mancuso F, Ferro S, Monti SM, Buonanno M, Russo E, De Sarro G, De Simone G, Supuran CT, Gitto R Eur J Med Chem. 2018 Dec 1;163:443-452. doi: 10.1016/j.ejmech.2018.11.073. PMID:30530195 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 6h33, resolution 1.58Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image