4ww6

Crystal structure of human carbonic anhydrase isozyme II with 2,3,5,6-Tetrafluoro-4-(propylthio)benzenesulfonamideCrystal structure of human carbonic anhydrase isozyme II with 2,3,5,6-Tetrafluoro-4-(propylthio)benzenesulfonamide

Structural highlights 4ww6 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , , , Related: 4wr7, 4wup, 4wuq Gene: CA2 (HUMAN) 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 Para substituted tetrafluorobenzenesulfonamides bind to carbonic anhydrases (CAs) extremely tightly and exhibit some of the strongest known protein-small ligand interactions, reaching an intrinsic affinity of 2 pM as determined by displacement isothermal titration calorimetry (ITC). The enthalpy and entropy of binding to five CA isoforms were measured by ITC in two buffers of different protonation enthalpies. The pKa values of compound sulfonamide groups were measured potentiometrically and spectrophotometrically, and enthalpies of protonation were measured by ITC in order to evaluate the proton linkage contributions to the observed binding thermodynamics. Intrinsic means the affinity of a sulfonamide anion for the Zn bound water form of CAs. Fluorination of the benzene ring significantly enhanced the observed affinities as it increased the fraction of deprotonated ligand while having little impact on intrinsic affinities. Intrinsic enthalpy contributions to the binding affinity were dominant over entropy and were more exothermic for CA I than for other CA isoforms. Thermodynamic measurements together with the X-ray crystallographic structures of protein-ligand complexes enabled analysis of structure-activity relationships in this enzyme ligand system. Intrinsic thermodynamics of 4-substituted-2,3,5,6-tetrafluorobenzenesulfonamide binding to carbonic anhydrases by isothermal titration calorimetry.,Zubriene A, Smirnoviene J, Smirnov A, Morkunaite V, Michailoviene V, Jachno J, Juozapaitiene V, Norvaisas P, Manakova E, Grazulis S, Matulis D Biophys Chem. 2015 Jun 6;205:51-65. doi: 10.1016/j.bpc.2015.05.009. PMID:26079542 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Carbonic anhydrase

spinqualitylabelsall models 4ww6, resolution 1.06Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image