Abstract
Cysteine proteinases play key roles in host-parasite interactions, including host invasion, parasite differentiation, and intracellular survival. Toxoplasma gondii expresses five cysteine proteases, including one cathepsin L‑like (TgCPL), one cathepsin B‑like (TgCPB) and three cathepsin C‑like (TgCPC1, 2 and 3) proteases. We performed the Structural modeling of catalytic domain of TgCPC1 with server I-TASSER, the template selected for homology modeling was Dipeptidyl peptidase I (Cathepsin C) (PDB code: 1JQP). The C-Score of structural modeling of catalytic domain was -0.5; in the L-domain there are nine ɑ-helices and two β-strands and in the right domain there are four β-strands and two ɑ-helices. Cys-440, His-651 and Asn-676, form the cysteine protease catalytic triad in the active site. Adjacent to active site there is a Tyr441 this residue may be involved in the binding of the N terminus of the peptide substrate. A tyrosine residue (Tyr 578) that binds a chloride ion in the crystal structures of rat and human Cathepsin C is also conserved.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Dou, Z., Carruthers, V.B.: Cathepsin proteases in toxoplasma gondii. In: Robinson, W.M., Dalton., J.P. (eds.) Cysteine Proteases of Pathogenic Organism, pp. 49–62. Landes Bioscience and Springer Science+Business Media (2011)
Rawlings, N.D., Barrett, A.J., Bateman, A.: MEROPS: the database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Res. 40(D1), D343–D350 (2011)
Sajid, M., McKerrow, J.: Cysteine Proteases of Parasitic Organism. Mol. Biochem. Parasitol. 120(1), 1–21 (2002)
Que, X., Engel, J.C., Ferguson, D., Wunderlinch, A., Tomavo, S.: Cathepsin Cs Are Key for the Intracellular Survival of the Protozoan Parasite, Toxoplasma gondii. The Journal of Biological Chemistry 282(7), 4994–5003 (2007)
Buchan, D.W., Ward, S.M., Lobley, A.E., Nugent, T.C., Bryson, K., Jones, D.T.: Protein annotation and modelling servers at University College London. Nucl. Acids Res. 38, W563–W568 (2010)
Zhang, Y.: I-TASSER server for protein 3D structure prediction. BMC Bioinformatics 9, 40 (2008)
de Castro, E., Sigrist, C.J., Gattiker, A., Bulliard, V., Langendijk-Genevaux, P.S., Gasteiger, E., Bairoch, A., Hulo, N.: ScanProsite: detection of PROSITE signaturematches and ProRule-associated functional and structural residues in proteins. Nucleic Acids Res. 1(34)(Web Server issue), 362–365 (2006) PubMed PMID: 16845026; PubMed Central PMCID: PMC1538847
Ivica, L., Doerks, T., Bork, P.: SMART 7: recent updates to the protein domain annotation resourse. Nucleic Acids Research 40, 302–305 (2012)
Hirokawa, T., Boon-Chieng, S., Mitaku, S.: SOSUI: classification and secondary structure prediction system for membrane proteins. Bioinformatics 14, 378–379 (1998)
Marchler-Bauer, A.: CDD: a Conserved Domain Database for the functional annotation of proteins. Nucleic Acids Res. 39(D), 225–229 (2011)
Ye, Y., Godzik, A.: Flexible structure alignment by chaining aligned fragment pairs allowing twists. Bioinformatics 19(suppl. 2), ii246–ii255 (2003)
Lovell, S.C., Davis, I.W., Arendall III, W.B., de Bakker, P.I.W., Word, J.M., Prisant, M.G., Richardson, J.S., Richardson, D.C.: Structure validation by Calpha geometry: phi,psi and Cbeta deviation. Proteins: Structure, Function & Genetics 50, 437–450 (2002)
Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C., Ferrin, T.E.: UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput. Chem. 25(13), 1605–1612 (2004)
Molgaard, A., Arnau, J., Lauritzen, C., Larsen, S., Petersen, G., Pedersen, J.: The crystal structure of human dipeptidyl peptidase I (Cathepsin C) in complex with the inhibitor Gly-Phe-CHN2. Biochem. J. 401, 645–650 (2007)
Larson, E.T., Parussini, F., Huynh, M.-H., Giebel, J., Kelley, A.M., Zhang, L., Carruthers, V.B.: Toxoplasma gondii Cathepsin L is the Primary Target of the Invasion- Inhibitory Compound Morpholinurea-leucyl-homophenyl-vinyl Sulfone Phenyl. Journal of Biological Chemistry 284(39), 26839–26850 (2009)
Que, X., Ngô, H., Lawton, J., Gray, M., Liu, Q., Engel, J., Reed, S.L.: The Cathepsin B of Toxoplasma gondii, Toxopain-1, Is Critical for Parasite Invasion and Rhoptry Protein Processing. The Journal of Biological Chemistry 277(28), 25791–25797 (2002)
Huang, R., Que, X., Hirata, K., Brinen, L.S., Lee, H.J., Hansell, E., Reed, S.: The Cathepsin L of Toxoplasma gondii (TgCPL) and its Endogenous Macromolecular Inhibitor, toxostantin. Mol. Biochem. Parasitol. 164(1), 86–94 (2009)
Giordanengo, L., Guinazu, N., Stempin, C., Fretes, R., Cerban, F., Gea, S.: Cruzipain, a major Tripanosoma cruzi antigen, Condictions the Host Immune Response in Favor of Parasite. Eur. J. Inmunol., 1003–1011 (2002)
Zhao, G., Zhou, A., Lv, G., Meng, M., Sun, M., Bai, Y., Sheyi, H.: Toxoplasma gondii cathepsin proteases are undeveloped prominent vaccine antigens against toxoplasmosis. BMC infectious Diseases 13(207) (2013)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer International Publishing Switzerland
About this paper
Cite this paper
León, M.M., Giraldo, D.M.M., Molina, D.A., Arenas, A.F., Gómez, J.E. (2014). Structural Modeling of Toxoplasma gondii TGME49_289620 Proteinase. In: Castillo, L., Cristancho, M., Isaza, G., Pinzón, A., Rodríguez, J. (eds) Advances in Computational Biology. Advances in Intelligent Systems and Computing, vol 232. Springer, Cham. https://doi.org/10.1007/978-3-319-01568-2_43
Download citation
DOI: https://doi.org/10.1007/978-3-319-01568-2_43
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-01567-5
Online ISBN: 978-3-319-01568-2
eBook Packages: EngineeringEngineering (R0)