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Article Draft - Carbonic anhydrase edit
Lead - β-CA edit
Article body edit
Structure
The beta class of carbonic anhydrase enzymes have a variety of subunits including dimeric, tetrameric and octomeric quaternary structures, which is in contrast to the alpha (α) and gamma (γ) forms which largely exist as monomers and trimers respectively.[1] Like many other carbonic anhydrases, the metal cofactor used in the β-carbonic anhydrase is a zinc atom. However, the β-carbonic anhydrase active site coordinates the metal ion using two cysteine residues and a histidine, as opposed to the usual arrangement of three histidine residues seen in the α, γ and δ-carbonic anhydrases.[1] Despite these differences in structure, the mechanism is largely conserved between the various classes of carbonic anhydrases.[1] To activate a water molecule for nucleophilic attack by a CO2 molecule, the water is coordinated by the zinc ion and then a highly conserved aspartate residue donates a hydrogen bond.[1] This aspartate residue along with an asparagine are highly conserved in the β-carbonic anhydrase and appear to be essential for catalytic activity as site directed mutagenesis of these residues dramatically reduces catalytic efficiency.[1]
Prevalence
The class of β-carbonic anhydrases is generally regarded as having the widest distribution of all the classes of Carbonic Anhydrase.[1] There is evidence for the β-carbonic anhydrases in most species of Bacteria, Archaea, plants and fungi.[1] In plants the carbonic anhydrase enzyme is expressed at high levels in green tissues and roots and can be found the following cellular locations: chloroplasts, cytoplasm and mitochondria.[1] The cytoplasmic and chlorplastic β-carbonic anhydrases have been linked to key cellular functions in plants such as carbon fixation and carbon dioxide accumulation.[1]
β-carbonic anhydrases have also been found to be highly prevalent in various species of invertebrates.[1] Some of the notable invertebrates found to contain the class of β-carbonic anhydrase were Drosophila, Placozoa, Cnidaria, Platyhelminthes, Nematoda, Arthropoda, Annelida, and Deuterostomia (namely in Hemichordata, Echinodermata, and Xenoturbellida).[1] Currently, there is no evidence for the presence of β-carbonic anhydrase genes in vertebrates and the evidence for their presence in Chordates is inconclusive.[1]
β-carbonic anhydrase in Drosophila melanogaster
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The first β-carbonic anhydrase found in an arthropod was found in Drosophila melanogaster, which is a widely used organism in research and is a representative organism of the animal kingdom.[1] Characterization of the β-carbonic anhydrase gene (DmBCA) in Drosophila melanogaster showed that the β class carbonic anhydrase predominantly functions as a mitochondrial enzyme.[1] Upon investigation of the kinetics for the β-carbonic anhydrase (DmBCA) in Drosophila melanogaster it was found that DmBCA has some of the highest catalytic efficiency seen in any class of carbonic anhydrase.[1] DmBCA has an experimental kcat of 9.5 × 105 s-1 and a kcat/Km of 1.1 × 108 M-1 s-1.[1]
β-carbonic anhydrase inhibitors
Owing to the presence of the beta class of carbonic anhydrases in many virulent species of bacteria and fungi, and their lack of representation in humans, usage of their inhibitors is being explored as novel therapeutics.[2] Diseases like Leprosy and Tuberculosis are caused by bacteria that utilize β-carbonic anhydrase as an essential part of their life cycle.[2] Tuberculosis has multiple drug resistant strains and thus new methods of treating the disease must be discovered.[2]
References edit
- ^ a b c d e f g h i j k l m n o p Syrjänen, Leo (2010). "Characterization of the first beta-class carbonic anhydrase from an arthropod (Drosophila melanogaster) and phylogenetic analysis of beta-class carbonic anhydrases in invertebrates". BMC Biochemistry. 11.
- ^ a b c Aspatwar, Ashok (8 November 2018). "Carbonic Anhydrase Inhibitors as Novel Drugs against Mycobacterial β-Carbonic Anhydrases: An Update on In Vitro and In Vivo Studies".
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