Comparison of the Sulfonamide Inhibition Profiles of the α-Carbonic Anhydrase Isoforms (SpiCA1, SpiCA2 and SpiCA3) Encoded by the Genome of the Scleractinian Coral Stylophora pistillata

Mar Drugs. 2019 Mar 1;17(3):146. doi: 10.3390/md17030146.

Abstract

The ubiquitous metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) are responsible for the reversible hydration of CO₂ to bicarbonate (HCO₃-) and protons (H⁺). Bicarbonate may subsequently generate carbonate used in many functional activities by marine organisms. CAs play a crucial role in several physiological processes, e.g., respiration, inorganic carbon transport, intra and extra-cellular pH regulation, and bio-mineralization. Multiple transcript variants and protein isoforms exist in the organisms. Recently, 16 α-CA isoforms have been identified in the coral Stylophora pistillata. Here, we focalized the interest on three coral isoforms: SpiCA1 and SpiCA2, localized in the coral-calcifying cells; and SpiCA3, expressed in the cytoplasm of the coral cell layers. The three recombinant enzymes were heterologously expressed and investigated for their inhibition profiles with sulfonamides and sulfamates. The three coral CA isoforms differ significantly in their susceptibility to inhibition with sulfonamides. This study provides new insights into the coral physiology and the comprehension of molecular mechanisms involved in the bio-mineralization processes, since CAs interact with bicarbonate transporters, accelerating the trans-membrane bicarbonate movement and modulating the pH at both sides of the plasma membranes.

Keywords: CA isoforms; biomineralization; carbonic anhydrases; corals CAs; recombinant enzyme; sulfonamides.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anthozoa / drug effects
  • Anthozoa / genetics
  • Anthozoa / metabolism*
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / genetics
  • Carbonic Anhydrases / isolation & purification
  • Carbonic Anhydrases / metabolism*
  • Genome
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / isolation & purification
  • Isoenzymes / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship
  • Sulfonamides / pharmacology*

Substances

  • Carbonic Anhydrase Inhibitors
  • Isoenzymes
  • Recombinant Proteins
  • Sulfonamides
  • Carbonic Anhydrases