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.
Most prokaryotic CAs as well as plant chloroplast CAs belong to
another, evolutionary distinct family of proteins, the β-family (see
<PDOC00586>).
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) |
| Sequences known to belong to this class detected by the profile: |
ALL |
| Other sequence(s) detected in Swiss-Prot: |
NONE. |
|
|
|
| Matching PDB structures:
12CA 1A42 1AM6 1AVN ... [ALL] |
| ALPHA_CA_1, PS00162; Alpha-carbonic anhydrases signature (PATTERN) |
| Consensus pattern: |
S-E-[HN]-x-[LIVM]-x(4)-[FYH]-x(2)-E-[LIVMGA]-H-[LIVMFA](2)
The second H is a zinc ligand |
| Sequences known to belong to this class detected by the pattern: |
ALL active CAs |
| Other sequence(s) detected in Swiss-Prot: |
NONE. |
|
|
|
| Matching PDB structures:
12CA 1A42 1AM6 1AVN ... [ALL] |
References
| 1 |
Authors |
Deutsch H.F. |
| Title |
Carbonic anhydrases. |
| Source |
Int. J. Biochem. 19:101-113(1987). |
| PubMed ID |
3106115 |
| 2 |
Authors |
Fernley R.T. |
| Title |
Non-cytoplasmic carbonic anhydrases. |
| Source |
Trends Biochem. Sci. 13:356-359(1988). |
| PubMed ID |
3149805 |
| 3 |
Authors |
Tashian R.E. |
| Title |
The carbonic anhydrases: widening perspectives on their evolution, expression and function. |
| Source |
BioEssays 10:186-192(1989). |
| PubMed ID |
2500929 |
| 4 |
Authors |
Edwards Y. |
| Title |
Structure and expression of mammalian carbonic anhydrases. |
| Source |
Biochem. Soc. Trans. 18:171-175(1990). |
| PubMed ID |
2116334 |
| 5 |
Authors |
Hewett-Emmett D., Tashian R.E. |
| Title |
Functional diversity, conservation, and convergence in the evolution of the alpha-, beta-, and gamma-carbonic anhydrase gene families. |
| Source |
Mol. Phylogenet. Evol. 5:50-77(1996). |
| PubMed ID |
8673298 |
| 6 |
Authors |
Leggat W., Dixon R., Saleh S., Yellowlees D. |
| Title |
A novel carbonic anhydrase from the giant clam Tridacna gigas contains two carbonic anhydrase domains. |
| Source |
FEBS J. 272:3297-3305(2005). |
| PubMed ID |
15978036 |
| DOI |
10.1111/j.1742-4658.2005.04742.x |
| 7 |
Authors |
Premkumar L., Greenblatt H.M., Bageshwar U.K., Savchenko T., Gokhman I., Sussman J.L., Zamir A. |
| Title |
Three-dimensional structure of a halotolerant algal carbonic anhydrase predicts halotolerance of a mammalian homolog. |
| Source |
Proc. Natl. Acad. Sci. U.S.A. 102:7493-7498(2005). |
| PubMed ID |
15894606 |
| DOI |
10.1073/pnas.0502829102 |
| 8 |
Authors |
Fujiwara S., Fukuzawa H., Tachiki A., Miyachi S. |
| Title |
Structure and differential expression of two genes encoding carbonic anhydrase in Chlamydomonas reinhardtii. |
| Source |
Proc. Natl. Acad. Sci. U.S.A. 87:9779-9783(1990). |
| PubMed ID |
2124702 |
| 9 |
Authors |
Huang S., Xue Y., Sauer-Eriksson E., Chirica L., Lindskog S., Jonsson B.H. |
| Title |
Crystal structure of carbonic anhydrase from Neisseria gonorrhoeae and its complex with the inhibitor acetazolamide. |
| Source |
J. Mol. Biol. 283:301-310(1998). |
| PubMed ID |
9761692 |
| 10 |
Authors |
Lindskog S. |
| Title |
Structure and mechanism of carbonic anhydrase. |
| Source |
Pharmacol. Ther. 74:1-20(1997). |
| PubMed ID |
9336012 |
| 11 |
Authors |
Whittington D.A., Waheed A., Ulmasov B., Shah G.N., Grubb J.H., Sly W.S., Christianson D.W. |
| Title |
Crystal structure of the dimeric extracellular domain of human carbonic anhydrase XII, a bitopic membrane protein overexpressed in certain cancer tumor cells. |
| Source |
Proc. Natl. Acad. Sci. U.S.A. 98:9545-9550(2001). |
| PubMed ID |
11493685 |
| DOI |
10.1073/pnas.161301298 |
Copyright
PROSITE is copyright. It is produced by the SIB Swiss Institute
Bioinformatics. There are no restrictions on its use by non-profit
institutions as long as its content is in no way modified. Usage by and
for commercial entities requires a license agreement. For information
about the licensing scheme send an email to
Prosite License
or
see:
prosite_license.html.
Miscellaneous
View entry in original PROSITE document format
View entry in raw text format (no links)
