Bioinformatic analysis of beta carbonic anhydrase sequences from protozoans and metazoans

Particle and Fibre Toxicology

Seppo Parkkila³  Csaba Ortutay²  Martti E E Tolvanen¹  Harlan Barker²  Reza Zolfaghari Emameh² 

[1] Department of Information Technology, University of Turku, 20520 Turku, Finland;Institute of Biomedical Technology and BioMediTech, University of Tampere, 33520 Tampere, Finland;Fimlab Ltd and Tampere University Hospital, Biokatu 4, 33520 Tampere, Finland

关键词: Protozoa;    Multiple sequence alignment;    Mitochondrial targeting peptide;    Metazoa;    Inhibitor;    Beta carbonic anhydrase;   

Others  :  814387
DOI  :  10.1186/1756-3305-7-38

 received in 2013-10-09, accepted in 2014-01-10,  发布年份 2014

【 摘 要 】

Background

Despite the high prevalence of parasitic infections, and their impact on global health and economy, the number of drugs available to treat them is extremely limited. As a result, the potential consequences of large-scale resistance to any existing drugs are a major concern. A number of recent investigations have focused on the effects of potential chemical inhibitors on bacterial and fungal carbonic anhydrases. Among the five classes of carbonic anhydrases (alpha, beta, gamma, delta and zeta), beta carbonic anhydrases have been reported in most species of bacteria, yeasts, algae, plants, and particular invertebrates (nematodes and insects). To date, there has been a lack of knowledge on the expression and molecular structure of beta carbonic anhydrases in metazoan (nematodes and arthropods) and protozoan species.

Methods

Here, the identification of novel beta carbonic anhydrases was based on the presence of the highly-conserved amino acid sequence patterns of the active site. A phylogenetic tree was constructed based on codon-aligned DNA sequences. Subcellular localization prediction for each identified invertebrate beta carbonic anhydrase was performed using the TargetP webserver.

Results

We verified a total of 75 beta carbonic anhydrase sequences in metazoan and protozoan species by proteome-wide searches and multiple sequence alignment. Of these, 52 were novel, and contained highly conserved amino acid residues, which are inferred to form the active site in beta carbonic anhydrases. Mitochondrial targeting peptide analysis revealed that 31 enzymes are predicted with mitochondrial localization; one was predicted to be a secretory enzyme, and the other 43 were predicted to have other undefined cellular localizations.

Conclusions

These investigations identified 75 beta carbonic anhydrases in metazoan and protozoan species, and among them there were 52 novel sequences that were not previously annotated as beta carbonic anhydrases. Our results will not only change the current information in proteomics and genomics databases, but will also suggest novel targets for drugs against parasites.

【 授权许可】

   
2014 Zolfaghari Emameh et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Elleuche S, Poggeler S: Carbonic anhydrases in fungi. Microbiology 2010, 156(Pt 1):23-29.
• [2]Huang S, Hainzl T, Grundstrom C, Forsman C, Samuelsson G, Sauer-Eriksson AE: Structural studies of beta-carbonic anhydrase from the green alga Coccomyxa: inhibitor complexes with anions and acetazolamide. PLoS One 2011, 6(12):e28458.
• [3]Supuran CT: Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat Rev Drug Discov 2008, 7(2):168-181.
• [4]Syrjanen L, Tolvanen M, Hilvo M, Olatubosun A, Innocenti A, Scozzafava A, Leppiniemi J, Niederhauser B, Hytonen VP, Gorr TA, et al.: Characterization of the first beta-class carbonic anhydrase from an arthropod (Drosophila melanogaster) and phylogenetic analysis of beta-class carbonic anhydrases in invertebrates. BMC Biochem 2010, 11:28. BioMed Central Full Text
• [5]Tripp BC, Smith K, Ferry JG: Carbonic anhydrase: new insights for an ancient enzyme. J Biol Chem 2001, 276(52):48615-48618.
• [6]Elleuche S, Poggeler S: Evolution of carbonic anhydrases in fungi. Curr Genet 2009, 55(2):211-222.
• [7]Esbaugh AJ, Tufts BL: The structure and function of carbonic anhydrase isozymes in the respiratory system of vertebrates. Respir Physiol Neurobiol 2006, 154(1–2):185-198.
• [8]Lane TW, Saito MA, George GN, Pickering IJ, Prince RC, Morel FM: Biochemistry: a cadmium enzyme from a marine diatom. Nature 2005, 435(7038):42.
• [9]Xu Y, Feng L, Jeffrey PD, Shi Y, Morel FM: Structure and metal exchange in the cadmium carbonic anhydrase of marine diatoms. Nature 2008, 452(7183):56-61.
• [10]Ferry JG: The gamma class of carbonic anhydrases. Biochim Biophys Acta 2010, 1804(2):374-381.
• [11]Alterio V, Vitale RM, Monti SM, Pedone C, Scozzafava A, Cecchi A, De Simone G, Supuran CT: Carbonic anhydrase inhibitors: X-ray and molecular modeling study for the interaction of a fluorescent antitumor sulfonamide with isozyme II and IX. J Am Chem Soc 2006, 128(25):8329-8335.
• [12]Nishimori I, Minakuchi T, Onishi S, Vullo D, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. DNA cloning, characterization, and inhibition studies of the human secretory isoform VI, a new target for sulfonamide and sulfamate inhibitors. J Med Chem 2007, 50(2):381-388.
• [13]Vullo D, Franchi M, Gallori E, Antel J, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of mitochondrial isozyme V with aromatic and heterocyclic sulfonamides. J Med Chem 2004, 47(5):1272-1279.
• [14]Vullo D, Innocenti A, Nishimori I, Pastorek J, Scozzafava A, Pastorekova S, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of the transmembrane isozyme XII with sulfonamides-a new target for the design of antitumor and antiglaucoma drugs? Bioorg Med Chem Lett 2005, 15(4):963-969.
• [15]Neish AC: Studies on chloroplasts: Their chemical composition and the distribution of certain metabolites between the chloroplasts and the remainder of the leaf. Biochem J 1939, 33(3):300-308.
• [16]Burnell JN, Gibbs MJ, Mason JG: Spinach chloroplastic carbonic anhydrase: nucleotide sequence analysis of cDNA. Plant Physiol 1990, 92(1):37-40.
• [17]Rowlett RS: Structure and catalytic mechanism of the beta-carbonic anhydrases. Biochim Biophys Acta 2010, 1804(2):362-373.
• [18]Fett JP, Coleman JR: Characterization and expression of two cDNAs encoding carbonic anhydrase in Arabidopsis thaliana. Plant Physiol 1994, 105(2):707-713.
• [19]Majeau N, Coleman JR: Nucleotide sequence of a complementary DNA encoding tobacco chloroplastic carbonic anhydrase. Plant Physiol 1992, 100(2):1077-1078.
• [20]Cronk JD, Endrizzi JA, Cronk MR, O’Neill JW, Zhang KY: Crystal structure of E. coli beta-carbonic anhydrase, an enzyme with an unusual pH-dependent activity. Protein Sci 2001, 10(5):911-922.
• [21]Guilloton MB, Korte JJ, Lamblin AF, Fuchs JA, Anderson PM: Carbonic anhydrase in Escherichia coli. A product of the cyn operon. J Biol Chem 1992, 267(6):3731-3734.
• [22]Smith KS, Ferry JG: A plant-type (beta-class) carbonic anhydrase in the thermophilic methanoarchaeon Methanobacterium thermoautotrophicum. J Bacteriol 1999, 181(20):6247-6253.
• [23]Rowlett RS, Tu C, Lee J, Herman AG, Chapnick DA, Shah SH, Gareiss PC: Allosteric site variants of Haemophilus influenzae beta-carbonic anhydrase. Biochemistry 2009, 48(26):6146-6156.
• [24]Supuran CT: Bacterial carbonic anhydrases as drug targets: toward novel antibiotics? Front Pharmacol 2011, 2:34.
• [25]Joseph P, Turtaut F, Ouahrani-Bettache S, Montero JL, Nishimori I, Minakuchi T, Vullo D, Scozzafava A, Kohler S, Winum JY, et al.: Cloning, characterization, and inhibition studies of a beta-carbonic anhydrase from Brucella suis. J Med Chem 2010, 53(5):2277-2285.
• [26]Burghout P, Vullo D, Scozzafava A, Hermans PW, Supuran CT: Inhibition of the beta-carbonic anhydrase from Streptococcus pneumoniae by inorganic anions and small molecules: Toward innovative drug design of antiinfectives? Bioorg Med Chem 2011, 19(1):243-248.
• [27]Vullo D, Nishimori I, Minakuchi T, Scozzafava A, Supuran CT: Inhibition studies with anions and small molecules of two novel beta-carbonic anhydrases from the bacterial pathogen Salmonella enterica serovar Typhimurium. Bioorg Med Chem Lett 2011, 21(12):3591-3595.
• [28]Abuaita BH, Withey JH: Bicarbonate Induces Vibrio cholerae virulence gene expression by enhancing ToxT activity. Infect Immun 2009, 77(9):4111-4120.
• [29]Kovacikova G, Lin W, Skorupski K: The LysR-type virulence activator AphB regulates the expression of genes in Vibrio cholerae in response to low pH and anaerobiosis. J Bacteriol 2010, 192(16):4181-4191.
• [30]Klengel T, Liang WJ, Chaloupka J, Ruoff C, Schroppel K, Naglik JR, Eckert SE, Mogensen EG, Haynes K, Tuite MF, et al.: Fungal adenylyl cyclase integrates CO2 sensing with cAMP signaling and virulence. Curr Biol 2005, 15(22):2021-2026.
• [31]Innocenti A, Leewattanapasuk W, Muhlschlegel FA, Mastrolorenzo A, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of the beta-class enzyme from the pathogenic yeast Candida glabrata with anions. Bioorg Med Chem Lett 2009, 19(16):4802-4805.
• [32]Bahn YS, Cox GM, Perfect JR, Heitman J: Carbonic anhydrase and CO2 sensing during Cryptococcus neoformans growth, differentiation, and virulence. Curr Biol 2005, 15(22):2013-2020.
• [33]Elleuche S, Poggeler S: A cyanase is transcriptionally regulated by arginine and involved in cyanate decomposition in Sordaria macrospora. Fungal Genet Biol 2008, 45(11):1458-1469.
• [34]Amoroso G, Morell-Avrahov L, Muller D, Klug K, Sultemeyer D: The gene NCE103 (YNL036w) from Saccharomyces cerevisiae encodes a functional carbonic anhydrase and its transcription is regulated by the concentration of inorganic carbon in the medium. Mol Microbiol 2005, 56(2):549-558.
• [35]Cleves AE, Cooper DN, Barondes SH, Kelly RB: A new pathway for protein export in Saccharomyces cerevisiae. J Cell Biol 1996, 133(5):1017-1026.
• [36]Gotz R, Gnann A, Zimmermann FK: Deletion of the carbonic anhydrase-like gene NCE103 of the yeast Saccharomyces cerevisiae causes an oxygen-sensitive growth defect. Yeast 1999, 15(10A):855-864.
• [37]So AK, Espie GS: Cloning, characterization and expression of carbonic anhydrase from the cyanobacterium Synechocystis PCC6803. Plant Mol Biol 1998, 37(2):205-215.
• [38]Sawaya MR, Cannon GC, Heinhorst S, Tanaka S, Williams EB, Yeates TO, Kerfeld CA: The structure of beta-carbonic anhydrase from the carboxysomal shell reveals a distinct subclass with one active site for the price of two. J Biol Chem 2006, 281(11):7546-7555.
• [39]Eriksson M, Karlsson J, Ramazanov Z, Gardestrom P, Samuelsson G: Discovery of an algal mitochondrial carbonic anhydrase: molecular cloning and characterization of a low-CO2-induced polypeptide in Chlamydomonas reinhardtii. Proc Natl Acad Sci U S A 1996, 93(21):12031-12034.
• [40]Mitsuhashi S, Mizushima T, Yamashita E, Yamamoto M, Kumasaka T, Moriyama H, Ueki T, Miyachi S, Tsukihara T: X-ray structure of beta-carbonic anhydrase from the red alga, Porphyridium purpureum, reveals a novel catalytic site for CO(2) hydration. J Biol Chem 2000, 275(8):5521-5526.
• [41]Fasseas MK, Tsikou D, Flemetakis E, Katinakis P: Molecular and biochemical analysis of the beta class carbonic anhydrases in Caenorhabditis elegans. Mol Biol Rep 2010, 37(6):2941-2950.
• [42]Guilloton MB, Lamblin AF, Kozliak EI, Gerami-Nejad M, Tu C, Silverman D, Anderson PM, Fuchs JA: A physiological role for cyanate-induced carbonic anhydrase in Escherichia coli. J Bacteriol 1993, 175(5):1443-1451.
• [43]Nishimori I, Onishi S, Takeuchi H, Supuran CT: The alpha and beta classes carbonic anhydrases from Helicobacter pylori as novel drug targets. Curr Pharm Des 2008, 14(7):622-630.
• [44]Mitsuhashi S, Ohnishi J, Hayashi M, Ikeda M: A gene homologous to beta-type carbonic anhydrase is essential for the growth of Corynebacterium glutamicum under atmospheric conditions. Appl Microbiol Biotechnol 2004, 63(5):592-601.
• [45]Fukuzawa H, Suzuki E, Komukai Y, Miyachi S: A gene homologous to chloroplast carbonic anhydrase (icfA) is essential to photosynthetic carbon dioxide fixation by Synechococcus PCC7942. Proc Natl Acad Sci U S A 1992, 89(10):4437-4441.
• [46]Merlin C, Masters M, McAteer S, Coulson A: Why is carbonic anhydrase essential to Escherichia coli? J Bacteriol 2003, 185(21):6415-6424.
• [47]Majeau N, Coleman JR: Effect of CO2 Concentration on Carbonic Anhydrase and Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase Expression in Pea. Plant Physiol 1996, 112(2):569-574.
• [48]Tetu SG, Tanz SK, Vella N, Burnell JN, Ludwig M: The Flaveria bidentis beta-carbonic anhydrase gene family encodes cytosolic and chloroplastic isoforms demonstrating distinct organ-specific expression patterns. Plant Physiol 2007, 144(3):1316-1327.
• [49]Ludwig M: The molecular evolution of beta-carbonic anhydrase in Flaveria. J Exp Bot 2011, 62(9):3071-3081.
• [50]Zabaleta E, Martin MV, Braun HP: A basal carbon concentrating mechanism in plants? Plant Sci: Int J Exp Plant Biol 2012, 187:97-104.
• [51]Kimber MS, Pai EF: The active site architecture of Pisum sativum beta-carbonic anhydrase is a mirror image of that of alpha-carbonic anhydrases. EMBO J 2000, 19(7):1407-1418.
• [52]Mitsuhashi S, Mizushima T, Yamashita E, Miyachi S, Tsukihara T: Crystallization and preliminary X-ray diffraction studies of a beta-carbonic anhydrase from the red alga Porphyridium purpureum. Acta Crystallogr D Biol Crystallogr 2000, 56(Pt 2):210-211.
• [53]Waterhouse AM, Procter JB, Martin DM, Clamp M, Barton GJ: Jalview Version 2–a multiple sequence alignment editor and analysis workbench. Bioinformatics 2009, 25(9):1189-1191.
• [54]Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, Lopez R, McWilliam H, Remmert M, Soding J, et al.: Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 2011, 7:539.
• [55]Suyama M, Torrents D, Bork P: PAL2NAL: robust conversion of protein sequence alignments into the corresponding codon alignments. Nucleic Acids Res 2006, 34:W609-W612. eb Server issue
• [56]Ronquist F, Teslenko M, Van der Mark P, Ayres DL, Darling A, Hohna S, Larget B, Liu L, Suchard MA, Huelsenbeck JP: MrBayes 3.2: efficient Bayesian phylogenetic inference and model choice across a large model space. Syst Biol 2012, 61(3):539-542.
• [57]Brown SD, Podar M, Klingeman DM, Johnson CM, Yang ZK, Utturkar SM, Land ML, Mosher JJ, Hurt RA Jr, Phelps TJ, et al.: Draft genome sequences for two metal-reducing Pelosinus fermentans strains isolated from a Cr(VI)-contaminated site and for type strain R7. J Bacteriol 2012, 194(18):5147-5148.
• [58]Guindon S, Dufayard JF, Lefort V, Anisimova M, Hordijk W, Gascuel O: New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Systematic biology 2010, 59(3):307-321.
• [59]Emanuelsson O, Nielsen H, Brunak S, von Heijne G: Predicting subcellular localization of proteins based on their N-terminal amino acid sequence. J Mol Biol 2000, 300(4):1005-1016.
• [60]Woese CR: Interpreting the universal phylogenetic tree. Proc Natl Acad Sci U S A 2000, 97(15):8392-8396.
• [61]Fabre N, Reiter IM, Becuwe-Linka N, Genty B, Rumeau D: Characterization and expression analysis of genes encoding alpha and beta carbonic anhydrases in Arabidopsis. Plant Cell Environ 2007, 30(5):617-629.
• [62]Mitra M, Lato SM, Ynalvez RA, Xiao Y, Moroney JV: Identification of a new chloroplast carbonic anhydrase in Chlamydomonas reinhardtii. Plant Physiol 2004, 135(1):173-182.
• [63]Bahn YS, Muhlschlegel FA: CO2 sensing in fungi and beyond. Curr Opin Microbiol 2006, 9(6):572-578.
• [64]Shah GN, Rubbelke TS, Hendin J, Nguyen H, Waheed A, Shoemaker JD, Sly WS: Targeted mutagenesis of mitochondrial carbonic anhydrases VA and VB implicates both enzymes in ammonia detoxification and glucose metabolism. Proc Natl Acad Sci U S A 2013, 110(18):7423-7428.
• [65]Fleige T, Pfaff N, Gross U, Bohne W: Localisation of gluconeogenesis and tricarboxylic acid (TCA)-cycle enzymes and first functional analysis of the TCA cycle in Toxoplasma gondii. Int J Parasit 2008, 38(10):1121-1132.
• [66]Hazen SA, Waheed A, Sly WS, LaNoue KF, Lynch CJ: Differentiation-dependent expression of CA V and the role of carbonic anhydrase isozymes in pyruvate carboxylation in adipocytes. FASEB J 1996, 10(4):481-490.
• [67]Ramakrishnan S, Serricchio M, Striepen B, Butikofer P: Lipid synthesis in protozoan parasites: A comparison between kinetoplastids and apicomplexans. Prog Lipid Res 2013, 52(4):488-512.
• [68]Murakami H, Sly WS: Purification and characterization of human salivary carbonic anhydrase. J Biol Chem 1987, 262(3):1382-1388.
• [69]Juhn J, Naeem-Ullah U, Maciel Guedes BA, Majid A, Coleman J, Paolucci Pimenta PF, Akram W, James AA, Marinotti O: Spatial mapping of gene expression in the salivary glands of the dengue vector mosquito, Aedes aegypti. Parasit Vectors 2011, 4:1. BioMed Central Full Text
• [70]Moreira-Ferro CK, Marinotti O, Bijovsky AT: Morphological and biochemical analyses of the salivary glands of the malaria vector, Anopheles darlingi. Tissue Cell 1999, 31(3):264-273.
• [71]Maresca A, Scozzafava A, Kohler S, Winum JY, Supuran CT: Inhibition of beta-carbonic anhydrases from the bacterial pathogen Brucella suis with inorganic anions. J Inorg Biochem 2012, 110:36-39.
• [72]Isik S, Guler OO, Kockar F, Aydin M, Arslan O, Supuran CT: Saccharomyces cerevisiae beta-carbonic anhydrase: inhibition and activation studies. Curr Pharm Des 2010, 16(29):3327-3336.
• [73]Isik S, Kockar F, Aydin M, Arslan O, Guler OO, Innocenti A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of the beta-class enzyme from the yeast Saccharomyces cerevisiae with sulfonamides and sulfamates. Bioorg Med Chem 2009, 17(3):1158-1163.
• [74]Monti SM, Maresca A, Viparelli F, Carta F, De Simone G, Muhlschlegel FA, Scozzafava A, Supuran CT: Dithiocarbamates are strong inhibitors of the beta-class fungal carbonic anhydrases from Cryptococcus neoformans, Candida albicans and Candida glabrata. Bioorg Med Chem Lett 2012, 22(2):859-862.
• [75]Guzel O, Maresca A, Hall RA, Scozzafava A, Mastrolorenzo A, Muhlschlegel FA, Supuran CT: Carbonic anhydrase inhibitors. The beta-carbonic anhydrases from the fungal pathogens Cryptococcus neoformans and Candida albicans are strongly inhibited by substituted-phenyl-1H-indole-5-sulfonamides. Bioorg Med Chem Lett 2010, 20(8):2508-2511.