1dca

STRUCTURE OF AN ENGINEERED METAL BINDING SITE IN HUMAN CARBONIC ANHYDRASE II REVEALS THE ARCHITECTURE OF A REGULATORY CYSTEINE SWITCHSTRUCTURE OF AN ENGINEERED METAL BINDING SITE IN HUMAN CARBONIC ANHYDRASE II REVEALS THE ARCHITECTURE OF A REGULATORY CYSTEINE SWITCH

Structural highlights 1dca is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 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 X-ray crystallographic analysis of the Thr-199-->Cys (T199C) variant of human carbonic anhydrase II reveals the first high-resolution structure of an engineered zinc coordination polyhedron in a metalloenzyme. In the wild-type enzyme, Thr-199 accepts a hydrogen bond from zinc-bound hydroxide; in the variant, the polypeptide backbone is sufficiently plastic to permit Cys-199 to displace hydroxide ion and coordinate to zinc with nearly perfect coordination stereochemistry. Importantly, the resulting His3-Cys-Zn2+ motif binds zinc more tightly than the wild-type enzyme [Kiefer, L. L., Krebs, J. F., Paterno, S. A., & Fierke C. A. (1993) Biochemistry (preceding paper in this issue)]. This novel zinc coordination polyhedron is analogous to that postulated for matrix metalloproteinase zymogens such as prostromelysin, where a cysteine-zinc interaction is responsible for the inactivity of the zymogen. Intriguingly, Cys-199 of T199C CAII is displaced from zinc coordination by soaking crystals in high concentrations of acetazolamide. Hence, residual catalytic activity measured for this variant probably arises from an alternate conformer of Cys-199 which allows the catalytic nucleophile, hydroxide ion, to be activated by zinc coordination. Structure of an engineered His3Cys zinc binding site in human carbonic anhydrase II.,Ippolito JA, Christianson DW Biochemistry. 1993 Sep 28;32(38):9901-5. PMID:8399159 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Carbonic anhydrase

spinqualitylabelsall models 1dca, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image