{PDOC00146} {PS00162; ALPHA_CA_1} {PS51144; ALPHA_CA_2} {BEGIN} *************************************************** * Alpha-carbonic anhydrases signature and profile * *************************************************** 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 (alpha, beta, gamma, delta and epsilon) that have no significant sequence identity and were invented independently. The alpha-CAs are found predominantly in animals but also in bacteria and green algae [5,6,7]. To date 15 alpha-CA or alpha-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 alpha-type CA. The dominating secondary structure is a 10-stranded, twisted beta-sheet, which divides the molecules into two halves (see ). Except for two pairs of parallel strands, the beta sheet is antiparallel. A few relatively short helices are located on the surface of the molecule [10]. Alpha-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 ). We derived a signature pattern for the alpha-CAs which includes one of the zinc-binding histidines. We also developed a profile that covers the entire alpha-CA catalytic domain. -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. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Note: Most prokaryotic CAs as well as plant chloroplast CAs belong to another, evolutionary distinct family of proteins, the beta-family (see ). -Last update: August 2005 / Text revised; profile added. [ 1] Deutsch H.F. "Carbonic anhydrases." Int. J. Biochem. 19:101-113(1987). PubMed=3106115 [ 2] Fernley R.T. "Non-cytoplasmic carbonic anhydrases." Trends Biochem. Sci. 13:356-359(1988). PubMed=3149805 [ 3] Tashian R.E. "The carbonic anhydrases: widening perspectives on their evolution, expression and function." BioEssays 10:186-192(1989). PubMed=2500929 [ 4] Edwards Y. "Structure and expression of mammalian carbonic anhydrases." Biochem. Soc. Trans. 18:171-175(1990). PubMed=2116334 [ 5] Hewett-Emmett D., Tashian R.E. "Functional diversity, conservation, and convergence in the evolution of the alpha-, beta-, and gamma-carbonic anhydrase gene families." Mol. Phylogenet. Evol. 5:50-77(1996). PubMed=8673298 [ 6] Leggat W., Dixon R., Saleh S., Yellowlees D. "A novel carbonic anhydrase from the giant clam Tridacna gigas contains two carbonic anhydrase domains." FEBS J. 272:3297-3305(2005). PubMed=15978036; DOI=10.1111/j.1742-4658.2005.04742.x [ 7] Premkumar L., Greenblatt H.M., Bageshwar U.K., Savchenko T., Gokhman I., Sussman J.L., Zamir A. "Three-dimensional structure of a halotolerant algal carbonic anhydrase predicts halotolerance of a mammalian homolog." Proc. Natl. Acad. Sci. U.S.A. 102:7493-7498(2005). PubMed=15894606; DOI=10.1073/pnas.0502829102 [ 8] Fujiwara S., Fukuzawa H., Tachiki A., Miyachi S. "Structure and differential expression of two genes encoding carbonic anhydrase in Chlamydomonas reinhardtii." Proc. Natl. Acad. Sci. U.S.A. 87:9779-9783(1990). PubMed=2124702 [ 9] Huang S., Xue Y., Sauer-Eriksson E., Chirica L., Lindskog S., Jonsson B.H. "Crystal structure of carbonic anhydrase from Neisseria gonorrhoeae and its complex with the inhibitor acetazolamide." J. Mol. Biol. 283:301-310(1998). PubMed=9761692 [10] Lindskog S. "Structure and mechanism of carbonic anhydrase." Pharmacol. Ther. 74:1-20(1997). PubMed=9336012 [11] Whittington D.A., Waheed A., Ulmasov B., Shah G.N., Grubb J.H., Sly W.S., Christianson D.W. "Crystal structure of the dimeric extracellular domain of human carbonic anhydrase XII, a bitopic membrane protein overexpressed in certain cancer tumor cells." Proc. Natl. Acad. Sci. U.S.A. 98:9545-9550(2001). PubMed=11493685; DOI=10.1073/pnas.161301298 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}