1h9n

H119N CARBONIC ANHYDRASE II

spinqualitylabelsall models 1h9n, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1h9n 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. Method: X-ray diffraction, Resolution 1.85Å Ligands: ZN 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 The catalytic zinc ion of human carbonic anhydrase II (CAII) is coordinated by three histidine ligands (H94, H96, and H119) and a hydroxide ion with tetrahedral geometry. Structural and functional analysis of variants in which the zinc ligands H94 and H119 are substituted with asparagine and glutamine, and comparison with results obtained with aspartate and glutamate substitutions indicate that the neutral ligand field provided by the protein optimizes the electrostatic environment for the catalytic function of the metal ion, including stabilization of bound anions. This is demonstrated by catalytic activity measurements for ester hydrolysis and CO2 hydration, as well as sulfonamide inhibitor affinity assays. High-resolution X-ray crystal structure determinations of H94N, H119N, and H119Q CAIIs reveal that the engineered carboxamide side chains coordinate to zinc with optimal stereochemistry. However, zinc coordination geometry remains tetrahedral only in H119Q CAII. Metal geometry changes to trigonal bipyramidal in H119N CAII due to the addition of a second water molecule to the zinc coordination polyhedron and also in H94N CAII due to the displacement of zinc-bound hydroxide by the bidentate coordination of a Tris molecule. Possibly, the bulky histidine imidazole ligands of the native enzyme play a role in disfavoring trigonal bipyramidal coordination geometry for zinc. Protein-metal affinity is significantly compromised by all histidine --> carboxamide ligand substitutions. Diminished affinity may result from significant movements (up to 1 A) of the metal ion from its position in the wild-type enzyme, as well as the associated, minor conformational changes of metal ligands and their neighboring residues. Histidine --> carboxamide ligand substitutions in the zinc binding site of carbonic anhydrase II alter metal coordination geometry but retain catalytic activity.,Lesburg CA, Huang C, Christianson DW, Fierke CA Biochemistry. 1997 Dec 16;36(50):15780-91. PMID:9398308 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Carbonic anhydrase 3D structures

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