Abstract
Carbonic anhydrase is a ubiquitous metalloenzyme, which catalyzes the reversible hydration of CO2 to HCO3− and H+. Metals play a key role in the bioactivity of this metalloenzyme, although their relationships with CA have not been completely clarified to date. The aim of this review is to explore the complexity and multi-aspect nature of these relationships, since metals can be cofactors of CA, but also inhibitors of CA activity and modulators of CA expression. Moreover, this work analyzes new insights and perspectives that allow translating new advances in basic science on the interaction between CA and metals to applications in several fields of research, ranging from biotechnology to environmental sciences.
Highlights
Carbonic anhydrase (CA) is a widely-distributed metalloenzyme, which catalyzes the reversible hydration of CO2 to HCO3 ́ and H+
Aerobic purification results in the loss of Fe3+ and substitution with Zn2+. These findings clearly suggest Fe2+ as the physiologically-relevant metal [22,23,24] in the active site of the CAM enzyme
N-terminal site can be effective in defending the native zinc(II)-(His)3 active site of CA, as well as other metalloproteins, from Cu2+ displacement, and in turn, inactivation [43]
Summary
Carbonic anhydrase (CA) is a widely-distributed metalloenzyme, which catalyzes the reversible hydration of CO2 to HCO3 ́ and H+ This biochemical reaction plays a key physiological role in diverse biological systems. Six distinct and unrelated CA families (α-, β-, γ-CA, δ, ζ and η-CAs) have been identified in animals, plants, algae and bacteria [1,2] They all catalyze the same reaction of CO2 hydration, but each family shows proper specific characteristics in primary amino acid sequence and 3D tertiary structure. The γ-anhydrase class is a homotrimer that has been described in bacteria, Archaea and plants [9] It includes a number of non-catalytically-active homologs present in diverse species. AAllll CCAA iissooeennzzyymmeess ccaattaallyyzzee tthhee rreevveerrssiibbllee hhyyddrraattiioonn ooff CCOO22 ttoo HHCCOO33 aanndd HH++ tthhrroouugghh aa mmeettaall--hhyyddrrooxxiiddee[L[Ligig3M3M22++((OOHH)) ́−]]mmeecchhaanniissmm [[1133––1155]]((FFigiguurere1)1.)T. Apart from zinc, other metals have been found to be physiologically-relevant cofactors of some CAs
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