PROSITE documentation PDOC00146

Alpha-carbonic anhydrases signature and profile




Description

Carbonic anhydrases (EC 4.2.1.1) (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) [6].

In the alga Chlamydomonas reinhardtii, two CA isozymes have been sequenced [8]. They are periplasmic glycoproteins evolutionary related to mammalian CAs. Some bacteria, such as Neisseria gonorrhoeae [9] 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 [10]. 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.

Note:

Most prokaryotic CAs as well as plant chloroplast CAs belong to another, evolutionary distinct family of proteins, the β-family (see <PDOC00586>).

Last update:

August 2005 / Text revised; profile added.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

ALPHA_CA_2, PS51144; Alpha-carbonic anhydrases profile  (MATRIX)

ALPHA_CA_1, PS00162; Alpha-carbonic anhydrases signature  (PATTERN)


References

1AuthorsDeutsch H.F.
TitleCarbonic anhydrases.
SourceInt. J. Biochem. 19:101-113(1987).
PubMed ID3106115

2AuthorsFernley R.T.
TitleNon-cytoplasmic carbonic anhydrases.
SourceTrends Biochem. Sci. 13:356-359(1988).
PubMed ID3149805

3AuthorsTashian R.E.
TitleThe carbonic anhydrases: widening perspectives on their evolution, expression and function.
SourceBioEssays 10:186-192(1989).
PubMed ID2500929

4AuthorsEdwards Y.
TitleStructure and expression of mammalian carbonic anhydrases.
SourceBiochem. Soc. Trans. 18:171-175(1990).
PubMed ID2116334

5AuthorsHewett-Emmett D., Tashian R.E.
TitleFunctional diversity, conservation, and convergence in the evolution of the alpha-, beta-, and gamma-carbonic anhydrase gene families.
SourceMol. Phylogenet. Evol. 5:50-77(1996).
PubMed ID8673298

6AuthorsLeggat W., Dixon R., Saleh S., Yellowlees D.
TitleA novel carbonic anhydrase from the giant clam Tridacna gigas contains two carbonic anhydrase domains.
SourceFEBS J. 272:3297-3305(2005).
PubMed ID15978036
DOI10.1111/j.1742-4658.2005.04742.x

7AuthorsPremkumar L., Greenblatt H.M., Bageshwar U.K., Savchenko T., Gokhman I., Sussman J.L., Zamir A.
TitleThree-dimensional structure of a halotolerant algal carbonic anhydrase predicts halotolerance of a mammalian homolog.
SourceProc. Natl. Acad. Sci. U.S.A. 102:7493-7498(2005).
PubMed ID15894606
DOI10.1073/pnas.0502829102

8AuthorsFujiwara S., Fukuzawa H., Tachiki A., Miyachi S.
TitleStructure and differential expression of two genes encoding carbonic anhydrase in Chlamydomonas reinhardtii.
SourceProc. Natl. Acad. Sci. U.S.A. 87:9779-9783(1990).
PubMed ID2124702

9AuthorsHuang S., Xue Y., Sauer-Eriksson E., Chirica L., Lindskog S., Jonsson B.H.
TitleCrystal structure of carbonic anhydrase from Neisseria gonorrhoeae and its complex with the inhibitor acetazolamide.
SourceJ. Mol. Biol. 283:301-310(1998).
PubMed ID9761692

10AuthorsLindskog S.
TitleStructure and mechanism of carbonic anhydrase.
SourcePharmacol. Ther. 74:1-20(1997).
PubMed ID9336012

11AuthorsWhittington D.A., Waheed A., Ulmasov B., Shah G.N., Grubb J.H., Sly W.S., Christianson D.W.
TitleCrystal structure of the dimeric extracellular domain of human carbonic anhydrase XII, a bitopic membrane protein overexpressed in certain cancer tumor cells.
SourceProc. Natl. Acad. Sci. U.S.A. 98:9545-9550(2001).
PubMed ID11493685
DOI10.1073/pnas.161301298



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