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Current Bioinformatics

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ISSN (Print): 1574-8936
ISSN (Online): 2212-392X

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Research Article

ProtPathDB: A Web-based Resource of Parasite Proteases

Author(s): Sadaf Shehzad, Rajan Pandey, Sushmita Sharma and Dinesh Gupta*

Volume 17, Issue 8, 2022

Published on: 22 August, 2022

Page: [710 - 722] Pages: 13

DOI: 10.2174/1574893617666220509185649

Price: $65

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Abstract

Background: Proteases regulate cell proliferation, cell growth, biological processes, and overall homeostasis. Several proteases are extensively annotated and well-characterized in pathogenic organisms such as bacteria, parasites, and microbial species as anti-bacterial, anti-parasitic and antimicrobial. Several of these proteins are being explored as viable targets for various drug discovery researches in various microbial diseases. Despite multiple studies on pathogen proteases, comprehensive information on pathogen proteases is scattered or redundant, if available.

Methods: We have developed a comprehensive and integrative protease database resource, Prot- PathDB, for 23 pathogen species distributed among five taxa, Amoebozoa, Apicomplexa, Heterolob osea, Kinetoplastida and Fungi. ProtPathDB collects and organizes sequences, class division, signal peptides, localization, post-translational modifications, three-dimensional structure and related structural information regarding binding sites, and binding scores of annotated proteases.

Results: The ProtPathDB is publicly available at http://bioinfo.icgeb.res.in/ProtPathDB.

Conclusion: We believe that the database will be a one-stop resource for integrative and comparative analysis of pathogen proteases to better understand the functions of the microbial proteases and help drug discovery efforts targeting proteases.

Keywords: Proteases, apicomplexan, database, Post-translational modification, prodomain, parasite.

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[1]
Neurath H, Walsh KA, Winter WP. Evolution of structure and function of proteases. Science 1967; 158(3809): 1638-44.
[http://dx.doi.org/10.1126/science.158.3809.1638] [PMID: 4862530]
[2]
López-Otín C, Bond JS. Proteases: Multifunctional enzymes in life and disease. J Biol Chem 2008; 283(45): 30433-7.
[http://dx.doi.org/10.1074/jbc.R800035200] [PMID: 18650443]
[3]
Salvesen GS, Hempel A, Coll NS. Protease signaling in animal and plant-regulated cell death. FEBS J 2016; 283(14): 2577-98.
[http://dx.doi.org/10.1111/febs.13616] [PMID: 26648190]
[4]
Li H, Child MA, Bogyo M. Proteases as regulators of pathogenesis: Examples from the Apicomplexa. Biochim Biophys Acta 2012; 1824(1): 177-85.
[5]
Rawlings ND. Protease Families, Evolution and Mechanism of Action Proteases: Structure and Function. Vienna: Springer Vienna 2013; pp. 1-36.
[http://dx.doi.org/10.1007/978-3-7091-0885-7_1]
[6]
Betanzos A, Bañuelos C, Orozco E. Host invasion by pathogenic Amoebae: Epithelial disruption by parasite proteins. Genes (Basel) 2019; 10(8): 618.
[http://dx.doi.org/10.3390/genes10080618] [PMID: 31416298]
[7]
Lam C, Jamerson M, Cabral G, Carlesso AM, Marciano-Cabral F. Expression of matrix metalloproteinases in Naegleria fowleri and their role in invasion of the central nervous system. Microbiology 2017; 163(10): 1436-44.
[http://dx.doi.org/10.1099/mic.0.000537] [PMID: 28954644]
[8]
Zyserman I, Mondal D, Sarabia F, McKerrow JH, Roush WR, Debnath A. Identification of cysteine protease inhibitors as new drug leads against Naegleria fowleri. Exp Parasitol 2018; 188: 36-41.
[http://dx.doi.org/10.1016/j.exppara.2018.03.010] [PMID: 29551628]
[9]
Rascón AA Jr, McKerrow JH. Synthetic and natural protease inhibitors provide insights into parasite development, virulence and pathogenesis. Curr Med Chem 2013; 20(25): 3078-102.
[http://dx.doi.org/10.2174/0929867311320250005] [PMID: 23514418]
[10]
Monroy VS, Flores OM, García CG, Maya YC, Fernández TD, Pérez Ishiwara DG. Calpain-like: A Ca2+ dependent cystein protease in Entamoeba histolytica cell death. Exp Parasitol 2015; 159: 245-51.
[http://dx.doi.org/10.1016/j.exppara.2015.10.005] [PMID: 26496790]
[11]
Alam MN, Das P, De T, Chakraborti T. Identification and characterization of a Leishmania donovani serine protease inhibitor: Possible role in regulation of host serine proteases. Life Sci 2016; 144: 218-25.
[http://dx.doi.org/10.1016/j.lfs.2015.12.004] [PMID: 26656469]
[12]
Alves CR, Souza RS, Charret KDS, et al. Understanding serine proteases implications on Leishmania spp lifecycle. Exp Parasitol 2018; 184: 67-81.
[http://dx.doi.org/10.1016/j.exppara.2017.11.008] [PMID: 29175018]
[13]
Bossard G, Cuny G, Geiger A. Secreted proteases of Trypanosoma brucei gambiense: Possible targets for sleeping sickness control? Biofactors 2013; 39(4): 407-14.
[http://dx.doi.org/10.1002/biof.1100] [PMID: 23553721]
[14]
Korde R, Bhardwaj A, Singh R, et al. A prodomain peptide of Plasmodium falciparum cysteine protease (falcipain-2) inhibits malaria parasite development. J Med Chem 2008; 51(11): 3116-23.
[http://dx.doi.org/10.1021/jm070735f] [PMID: 18461922]
[15]
Tanveer A, Allen SM, Jackson KE, Charan M, Ralph SA, Habib S. An FtsH protease Is recruited to the mitochondrion of Plasmodium falciparum. PLoS One 2013; 8: 74408.
[http://dx.doi.org/10.1371/journal.pone.0074408]
[16]
Klemba M, Goldberg DE. Characterization of plasmepsin V, a membrane-bound aspartic protease homolog in the endoplasmic reticulum of Plasmodium falciparum. Mol Biochem Parasitol 2005; 143(2): 183-91.
[http://dx.doi.org/10.1016/j.molbiopara.2005.05.015] [PMID: 16024107]
[17]
Deu E, Leyva MJ, Albrow VE, Rice MJ, Ellman JA, Bogyo M. Functional studies of Plasmodium falciparum dipeptidyl aminopeptidase I using small molecule inhibitors and active site probes. Chem Biol 2010; 17(8): 808-19.
[http://dx.doi.org/10.1016/j.chembiol.2010.06.007] [PMID: 20797610]
[18]
Shehzad S, Pandey R, Malhotra P, Gupta D. Computational design of novel allosteric inhibitors for Plasmodium falciparum DegP. Molecules 2021; 26(9): 2742.
[http://dx.doi.org/10.3390/molecules26092742] [PMID: 34066964]
[19]
Gao B-J, Mou Y-N, Tong S-M, Ying S-H, Feng M-G. Subtilisin-like Pr1 proteases marking the evolution of pathogenicity in a wide-spectrum insect-pathogenic fungus. Virulence 2020; 11(1): 365-80.
[http://dx.doi.org/10.1080/21505594.2020.1749487] [PMID: 32253991]
[20]
Kajfasz JK, Martinez AR, Rivera-Ramos I, et al. Role of Clp proteins in expression of virulence properties of Streptococcus mutans. J Bacteriol 2009; 191(7): 2060-8.
[http://dx.doi.org/10.1128/JB.01609-08] [PMID: 19181818]
[21]
Ruiz-Perez F, Nataro JP. Bacterial serine proteases secreted by the autotransporter pathway: Classification, specificity, and role in virulence. Cell Mol Life Sci 2014; 71(5): 745-70.
[http://dx.doi.org/10.1007/s00018-013-1355-8] [PMID: 23689588]
[22]
Lee JH, Ancona V, Zhao Y. Lon protease modulates virulence traits in Erwinia amylovora by direct monitoring of major regulators and indirectly through the Rcs and Gac-Csr regulatory systems. Mol Plant Pathol 2018; 19(4): 827-40.
[http://dx.doi.org/10.1111/mpp.12566] [PMID: 28509355]
[23]
Bhattacharjee S, Stahelin RV, Haldar K. Host targeting of virulence determinants and phosphoinositides in blood stage malaria parasites. Trends Parasitol 2012; 28(12): 555-62.
[http://dx.doi.org/10.1016/j.pt.2012.09.004] [PMID: 23084821]
[24]
Sanman LE, Bogyo M. Activity-based profiling of proteases. Annu Rev Biochem 2014; 83(1): 249-73.
[http://dx.doi.org/10.1146/annurev-biochem-060713-035352] [PMID: 24905783]
[25]
Hauske P, Ottmann C, Meltzer M, Ehrmann M, Kaiser M. Allosteric regulation of proteases. ChemBioChem 2008; 9(18): 2920-8.
[http://dx.doi.org/10.1002/cbic.200800528] [PMID: 19021141]
[26]
Rawlings ND, Barrett AJ, Thomas PD, Huang X, Bateman A, Finn RD. The MEROPS database of proteolytic enzymes, their substrates and inhibitors in 2017 and a comparison with peptidases in the PANTHER database. Nucleic Acids Res 2018; 46(D1): D624-32.
[http://dx.doi.org/10.1093/nar/gkx1134] [PMID: 29145643]
[27]
Pérez-Silva JG, Español Y, Velasco G, Quesada V. The Degradome database: Expanding roles of mammalian proteases in life and disease. Nucleic Acids Res 2016; 44(D1): D351-5.
[http://dx.doi.org/10.1093/nar/gkv1201] [PMID: 26553809]
[28]
Deu E. Proteases as antimalarial targets: Strategies for genetic, chemical, and therapeutic validation. FEBS J 2017; 284(16): 2604-28.
[http://dx.doi.org/10.1111/febs.14130] [PMID: 28599096]
[29]
Warrenfeltz S, Basenko EY, Crouch K, et al. EuPathDB: The Eukaryotic Pathogen Genomics Database Resource Eukaryotic Genomic Databases. New York, NY: Springer New York 2018. http://link.springer.com/10.1007/978-1-4939-7737-6_5
[30]
UniProt. The universal protein knowledgebase. Nucleic Acids Res 2017; 45(D1): D158-69.
[http://dx.doi.org/10.1093/nar/gkw1099] [PMID: 27899622]
[31]
Marchler-Bauer A, Lu S, Anderson JB, et al. CDD: A conserved domain database for the functional annotation of proteins Nucleic Acids Res 2011; 39(DATABASE): 225-9.
[http://dx.doi.org/10.1093/nar/gkq1189]
[32]
Quevillon E, Silventoinen V, Pillai S, et al. InterProScan: Protein domains identifier. Nucleic Acids Res 2005; 33(WEB SERVER): 116-20.
[http://dx.doi.org/10.1093/nar/gki442]
[33]
Agbowuro AA, Huston WM, Gamble AB, Tyndall JDA. Proteases and protease inhibitors in infectious diseases. Med Res Rev 2018; 38(4): 1295-331.
[http://dx.doi.org/10.1002/med.21475] [PMID: 29149530]
[34]
Li L, Stoeckert CJ Jr, Roos DS. OrthoMCL: Identification of ortholog groups for eukaryotic genomes. Genome Res 2003; 13(9): 2178-89.
[http://dx.doi.org/10.1101/gr.1224503] [PMID: 12952885]
[35]
Petersen TN, Brunak S, von Heijne G, Nielsen H. SignalP 4.0: Discriminating signal peptides from transmembrane regions. Nat Methods 2011; 8(10): 785-6.
[http://dx.doi.org/10.1038/nmeth.1701] [PMID: 21959131]
[36]
Predicting Subcellular Localization of Proteins Based on their Nterminal Amino Acid Sequence | Elsevier Enhanced Reader. 2011; 12.
[37]
Claros’ MG, Vincens P. Molkculaire L de Gc, Ura C. Computational method to predict mitochondri and their targeting sequences. Eur J Biochem 1996; 241(3): 779-86.
[38]
Duckert P, Brunak S, Blom N. Prediction of proprotein convertase cleavage sites. Protein Eng Des Sel 2004; 17(1): 107-12.
[http://dx.doi.org/10.1093/protein/gzh013] [PMID: 14985543]
[39]
Jacobson MP, Friesner RA, Xiang Z, Honig B. On the role of the crystal environment in determining protein side-chain conformations. J Mol Biol 2002; 320(3): 597-608.
[http://dx.doi.org/10.1016/S0022-2836(02)00470-9] [PMID: 12096912]
[40]
Jacobson MP, Pincus DL, Rapp CS, et al. A hierarchical approach to all-atom protein loop prediction. Proteins 2004; 55(2): 351-67.
[http://dx.doi.org/10.1002/prot.10613] [PMID: 15048827]
[41]
Halgren T. New method for fast and accurate binding-site identification and analysis. Chem Biol Drug Des 2007; 69(2): 146-8.
[http://dx.doi.org/10.1111/j.1747-0285.2007.00483.x] [PMID: 17381729]
[42]
Halgren TA. Identifying and characterizing binding sites and assessing drug ability. J Chem Inf Model 2009; 49(2): 377-89.
[http://dx.doi.org/10.1021/ci800324m] [PMID: 19434839]
[43]
Steentoft C, Vakhrushev SY, Joshi HJ, et al. Precision mapping of the human O-GalNAc glycoproteome through SimpleCell technology. EMBO J 2013; 32(10): 1478-88.
[http://dx.doi.org/10.1038/emboj.2013.79] [PMID: 23584533]
[44]
Gupta R, Brunak S. Prediction of glycosylation across the human proteome and the correlation to protein function. Pac Symp Biocomput 2002; 13: 310-22.
[45]
Blom N, Gammeltoft S, Brunak S. Sequence and structure-based prediction of eukaryotic protein phosphorylation sites. J Mol Biol 1999; 294(5): 1351-62.
[46]
Kumar TA. locBLAST v2.0 - an improved PHP library for embedding standalone NCBI BLAST+ program to an interactive graphical user interface. bioRxiv 2019.
[http://dx.doi.org/10.1101/556225]
[47]
Rawlings ND, Barrett AJ. Evolutionary families of peptidases. Biochem J 1993; 290(Pt 1): 205-18.
[http://dx.doi.org/10.1042/bj2900205] [PMID: 8439290]
[48]
Chen J-M, Rawlings ND, Stevens RAE, Barrett AJ. Identification of the active site of legumain links it to caspases, clostripain and gingipains in a new clan of cysteine endopeptidases. FEBS Lett 1998; 441(3): 361-5.
[49]
Turk D. Gunčar G, Podobnik M, Turk B. Revised definition of substrate binding sites of papain-like cysteine proteases. Biol Chem 1998; 379(2): 137-47.https://www.degruyter.com/document/doi/10.1515/bchm.1998.379.2.137/html
[http://dx.doi.org/10.1515/bchm.1998.379.2.137] [PMID: 9524065]
[50]
Hong L, Tang J. Flap position of free memapsin 2 (β-secretase), a model for flap opening in aspartic protease catalysis. Biochemistry 2004; 43(16): 4689-95.
[http://dx.doi.org/10.1021/bi0498252] [PMID: 15096037]
[51]
Fastrezx J, Fersht AR. Demonstration of the acyl-enzyme mechanism for the hydrolysis of peptides and anilides by chymotrypsint. Biochemistry 1973; 12(11): 2025-34.
[52]
Rao MB, Tanksale AM, Ghatge MS, Deshpande VV. Molecular and biotechnological aspects of microbial proteases. Microbiol Mol Biol Rev 1998; 62(3): 597-635.
[http://dx.doi.org/10.1128/MMBR.62.3.597-635.1998] [PMID: 9729602]
[53]
SeemOller E. Lupas A, Stock D, Lowe J, Huber R, Baumeister W. Proteasome from Thermoplasma acidophilum: A threonine proteas. Science 1995; 268(5210): 579-82.
[54]
Almagro Armenteros JJ, Tsirigos KD, Sønderby CK, et al. SignalP 5.0 improves signal peptide predictions using deep neural networks. Nat Biotechnol 2019; 37(4): 420-3.
[http://dx.doi.org/10.1038/s41587-019-0036-z] [PMID: 30778233]
[55]
Almagro Armenteros JJ, Salvatore M, Emanuelsson O, et al. Detecting sequence signals in targeting peptides using deep learning. Life Sci Alliance 2019; 2(5): e201900429.
[http://dx.doi.org/10.26508/lsa.201900429] [PMID: 31570514]
[56]
Bhuiyan MS, Fukunaga K. Activation of HtrA2, a mitochondrial serine protease mediates apoptosis: Current knowledge on HtrA2 mediated myocardial ischemia/reperfusion injury. Cardiovasc Ther 2008; 26(3): 224-32.
[http://dx.doi.org/10.1111/j.1755-5922.2008.00052.x] [PMID: 18786092]

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