Human Carbonic Anhydrase Isozyme

The same group further investigated human carbonic anhydrase isozyme II (hCAII), which is a 30 kDa protein [53]. The Zn ion is tetrahedraUy bound to the imidazole side chains of three histidines. The fourth Hgand can be either water or hydroxide. It was believed at the time that the nature of the fourth ligand would depend on pH value. If the argument were accepted, the Zn spectra of hCAII at pH 5 and 8.5 would look drastically different since the theoretical calculations of the EFG tensor based on the... 

A dynamic combinatorial library of six components can be generated under thermodynamic control by imine formation and exchange combined with non-covalent bonding within the enzyme binding site and DCL was evaluated for their relative affinities toward the physiologically relevant human carbonic anhydrase hCA I and hCA II isozymes [66]. 

K. K. Kannan, M. Ramanadham and T. A. Jones, Structure, refinement, and function of carbonic anhydrase isozymes refinement of human carbonic anhydrase I, Ann. N.Y Acad. Sci, 1984, 429, 49-60 (pdb 2cab). 

Human CAII (carbonic anhydrase isozyme II) ZnNsO 9.8 1 CP/QCPMG [53]... 

Bayram, E. Senturk, M. Kufrevioglu, O.I. Supuran, CT. (2008). In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II. Bioorganic and Medicinal Chemistry, 16,9101-9105. 

HCAII, one of seven isozymes of the zinc metallo-protein human carbonic anhydrase (HCA), is a 260 residue protein with a mass of 29 kDa. A single zinc atom is located in the enzyme active site and is necessary for catalytic activity. The active site itself lies at the bottom of a deep cavity (15 A deep) in the protein, which is readily accessible... 

Osteopetrosis (marble bone disease), characterized by increased bone density, is due to inability to resorb bone. One form occurs along with renal tubular acidosis and cerebral calcification. It is due to mutations in the gene (located on chromosome 8q22) encoding carbonic anhydrase II (CAII), one of four isozymes of carbonic anhydrase present in human tissues. The reaction catalyzed by carbonic anhydrase is shown below ... 

Carbonic anhydrase (CA) exists in three known soluble forms in humans. All three isozymes (CA I, CA II, and CA III) are monomeric, zinc metalloenzymes with a molecular weight of approximately 29,000. The enzymes catalyze the reaction for the reversible hydration of C02. The CA I deficiency is known to cause renal tubular acidosis and nerve deafness. Deficiency of CA II produces osteopetrosis, renal tubular acidosis, and cerebral calcification. More than 40 CA II-defi-cient patients with a wide variety of ethnic origins have been reported. Both syndromes are autosomal recessive disorders. Enzymatic confirmation can be made by quantitating the CA I and CA II levels in red blood cells. Normally, CA I and CAII each contribute about 50% of the total activity, and the CAI activity is completely abolished by the addition of sodium iodide in the assay system (S22). The cDNA and genomic DNA for human CA I and II have been isolated and sequenced (B34, M33, V9). Structural gene mutations, such as missense mutation, nonsense... 

Tempering C., Scozzafava, A., Puccetti, L., and Supuran, C. (2005). Carbonic anhydrase activators X-ray crystal structure of the adduct of human isozyme II with histidine as a platform for the design of stronger activators. Bioorg. Med. Chem. Lett. 15,5136-5141. 

The structure of carbonic anhydrase has been completely elucidated. Both the amino acid sequence and the three-dimensional structure of the crystalline enzyme are known. Actually, there are two isozymes, a low- and a high-activity form having been isolated from human erythrocytes, with the latter designated the C form (HCA-C). 

The best-smdied carbonic anhydrases are the bovine and human a-carbonic anhydrases. They exist as isozymes (enzymes with the same function, but slightly different amino acid sequence) and the focus is on the most abundant one - isozyme 11, abbreviated a-CAll. The bovine enzyme, isolated from red blood cells, is a byproduct of the meat industry. The human enzyme is a current drug target for glaucoma and a possible target for several other diseases (for a review see [29]). Fierke and coworkers cloned human a-CAll and expressed it in E. coli. Numerous mutants... 

Scozzafava, A. Supuran, C.T. (2002b). Carbonic Anhydrase Activators Human Isozyme II is Strongly Activated by Oligopeptides Incorporating the Carboxyterminal Sequence of the Bicarbonate Anion Exchanger AEl. Bioorganic Medicinal Chemistry Letters, 12,1177-1180. 

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