Carbonic anhydrases (EC 18.104.22.168) (CA) [1,2,3,4] are zinc metalloenzymes which
catalyze the reversible hydration of carbon dioxide, a reaction underlying
many diverse physiological processes in animals, plants, archaebacteria, and
eubacteria. Currently there are five evolutionarily distinct CA families
(α, β, γ, delta and epsilon) that have no significant sequence
identity and were invented independently. The α-CAs are found
predominantly in animals but also in bacteria and green algae [5,6,7].
To date 15 α-CA or α-CA-like proteins have been identified in mammals.
These can be divided into five broad subgroups: the cytosolic CAs (CA-I,
CA-II, CA-III, CA-VII and CA XIII), mitochondrial CAs (CA-VA and CA-VB),
secreted CAs (CA-VI), membrane-associated (CA-IV, CA-IX, CA-XII and CA-XIV)
and those without CA activity, the CA-related proteins (CA-RP VIII, X and XI)
In the alga Chlamydomonas reinhardtii, two CA isozymes have been sequenced
. They are periplasmic glycoproteins evolutionary related to mammalian CAs.
Some bacteria, such as Neisseria gonorrhoeae  also have an α-type CA.
The dominating secondary structure is a 10-stranded, twisted β-sheet, which
divides the molecules into two halves (see <PDB:1RAZ>). Except for two pairs
of parallel strands, the β sheet is antiparallel. A few relatively short
helices are located on the surface of the molecule . α-CAs contain a
single zinc atom bound to three conserved histidine residues. The
catalytically active group is the zinc-bound water which ionizes to a
hydroxide group. In the mechanism of catalysis, nucleophilic attack of CO2 by
a zinc-bound hydroxide ion is followed by displacement of the resulting zinc-bound bicarbonate ion by water; subsequent deprotonation regenerates the
nucleophilic zinc-bound hydroxide ion [5,11].
Protein D8 from Vaccinia and other poxviruses is related to CAs but has lost
two of the zinc-binding histidines as well as many otherwise conserved
residues. This is also true of the N-terminal extracellular domain of
some receptor-type tyrosine-protein phosphatases (see <PDOC00323>).
We derived a signature pattern for the α-CAs which includes one of the
zinc-binding histidines. We also developed a profile that covers the entire
α-CA catalytic domain.
Most prokaryotic CAs as well as plant chloroplast CAs belong to
another, evolutionary distinct family of proteins, the β-family (see
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