Recent advances and concepts in substrate specificity determination of proteases using tailored libraries of fluorogenic substrates with unnatural amino acids
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Wioletta Rut
, Paulina Kasperkiewicz , Anna Byzia , Marcin Poreba , Katarzyna Groborz and Marcin Drag
Abstract
Substrate specificity of proteases can be determined using several methods among which the most frequently used are positional scanning library, proteomics and phage display. Classic approaches can deliver information about preferences for natural amino acids in binding pockets of virtually all proteases. However, recent studies demonstrate the ability to obtain much more information by application of unnatural amino acids to positional scanning library approaches. This knowledge can be used for the design of more active and specific substrates, inhibitors and activity based probes. In this minireview we describe recent strategies and concepts for the design and application of fluorogenic substrates library tailored for exopeptidases and endopeptidases.
Acknowledgments
This work was supported by the National Science Centre grant 2011/03/B/ST5/01048 in Poland. The work was also supported by a statutory activity subsidy from the Polish Ministry of Science and Higher Education for the Faculty of Chemistry at Wroclaw University of Technology. We would like to thank Guy S. Salvesen for critical reading of the manuscript.
References
Backes, B.J., Harris, J.L., Leonetti, F., Craik, C.S., and Ellman, J.A. (2000). Synthesis of positional-scanning libraries of fluorogenic peptide substrates to define the extended substrate specificity of plasmin and thrombin. Nat. Biotechnol. 18, 187–193.10.1038/72642Search in Google Scholar PubMed
Berger, A.B., Sexton, K.B., and Bogyo, M. (2006). Commonly used caspase inhibitors designed based on substrate specificity profiles lack selectivity. Cell Res. 16, 961–963.10.1038/sj.cr.7310112Search in Google Scholar PubMed
Butler, G.S., Dean, R.A., Smith, D., and Overall, C.M. (2009). Membrane protease degradomics: proteomic identification and quantification of cell surface protease substrates. Methods Mol. Biol. 528, 159–176.10.1007/978-1-60327-310-7_12Search in Google Scholar PubMed
Byzia, A., Haeggstrom, J.Z., Salvesen, G.S., and Drag, M. (2014). A remarkable activity of human leukotriene A4 hydrolase (LTA4H) toward unnatural amino acids. Amino Acids 46, 1313–1320.10.1007/s00726-014-1694-2Search in Google Scholar PubMed PubMed Central
Carroll, R.K., Veillard, F., Gagne, D.T., Lindenmuth, J.M., Poreba, M., Drag, M., Potempa, J., and Shaw, L.N. (2013). The Staphylococcus aureus leucine aminopeptidase is localized to the bacterial cytosol and demonstrates a broad substrate range that extends beyond leucine. Biol. Chem. 394, 791–803.10.1515/hsz-2012-0308Search in Google Scholar PubMed PubMed Central
Choe, Y., Leonetti, F., Greenbaum, D.C., Lecaille, F., Bogyo, M., Bromme, D., Ellman, J.A., and Craik, C.S. (2006). Substrate profiling of cysteine proteases using a combinatorial peptide library identifies functionally unique specificities. J. Biol. Chem. 281, 12824–12832.10.1074/jbc.M513331200Search in Google Scholar PubMed
Diamond, S.L. (2007). Methods for mapping protease specificity. Curr. Opin. Chem. Biol. 11, 46–51.10.1016/j.cbpa.2006.11.021Search in Google Scholar PubMed
Dix, M.M., Simon, G.M., and Cravatt, B.F. (2008). Global mapping of the topography and magnitude of proteolytic events in apoptosis. Cell 134, 679–691.10.1016/j.cell.2008.06.038Search in Google Scholar PubMed PubMed Central
Doucet, A., Butler, G.S., Rodriguez, D., Prudova, A., and Overall, C.M. (2008). Metadegradomics: toward in vivo quantitative degradomics of proteolytic post-translational modifications of the cancer proteome. Mol. Cell Proteomics 7, 1925–1951.10.1074/mcp.R800012-MCP200Search in Google Scholar PubMed
Drag, M., and Salvesen, G.S. (2010). Emerging principles in protease-based drug discovery. Nat. Rev. Drug Discov. 9, 690–701.10.1038/nrd3053Search in Google Scholar PubMed PubMed Central
Drag, M., Bogyo, M., Ellman, J.A., and Salvesen, G.S. (2010). Aminopeptidase fingerprints, an integrated approach for identification of good substrates and optimal inhibitors. J. Biol. Chem. 285, 3310–3318.10.1074/jbc.M109.060418Search in Google Scholar PubMed PubMed Central
Gras, S., Byzia, A., Gilbert, F.B., McGowan, S., Drag, M., Silvestre, A., Niepceron, A., Lecaille, F., Lalmanach, G., and Brossier, F. (2014). Aminopeptidase N1 (EtAPN1), an M1 metalloprotease of the apicomplexan parasite Eimeria tenella, participates in parasite development. Eukaryot. Cell 13, 884–895.10.1128/EC.00062-14Search in Google Scholar PubMed PubMed Central
Gutmann, H.R., and Fruton, J.S. (1948). On the proteolytic enzymes of animal tissues; an intracellular enzyme related to chymotrypsin. J. Biol. Chem. 174, 851–858.10.1016/S0021-9258(18)57294-XSearch in Google Scholar
Harris, J.L., Backes, B.J., Leonetti, F., Mahrus, S., Ellman, J.A., and Craik, C.S. (2000). Rapid and general profiling of protease specificity by using combinatorial fluorogenic substrate libraries. Proc. Natl. Acad. Sci. USA 97, 7754–7759.10.1073/pnas.140132697Search in Google Scholar PubMed PubMed Central
Ito, K., Nakajima, Y., Onohara, Y., Takeo, M., Nakashima, K., Matsubara, F., Ito, T., and Yoshimoto, T. (2006). Crystal structure of aminopeptidase N (proteobacteria alanyl aminopeptidase) from Escherichia coli and conformational change of methionine 260 involved in substrate recognition. J. Biol. Chem. 281, 33664–33676.10.1074/jbc.M605203200Search in Google Scholar PubMed
Kasperkiewicz, P., Gajda, A.D., and Drag, M. (2012). Current and prospective applications of non-proteinogenic amino acids in profiling of proteases substrate specificity. Biol. Chem. 393, 843–851.10.1515/hsz-2012-0167Search in Google Scholar PubMed
Kasperkiewicz, P., Poreba, M., Snipas, S.J., Parker, H., Winterbourn, C.C., Salvesen, G.S., and Drag, M. (2014). Design of ultrasensitive probes for human neutrophil elastase through hybrid combinatorial substrate library profiling. Proc. Natl. Acad. Sci. USA 111, 2518–2523.10.1073/pnas.1318548111Search in Google Scholar PubMed PubMed Central
Kelly, J.A., Neidle, E.L., and Neidle, A. (1983). An aminopeptidase from mouse brain cytosol that cleaves N-terminal acidic amino acid residues. J. Neurochem. 40, 1727–1734.10.1111/j.1471-4159.1983.tb08148.xSearch in Google Scholar PubMed
Kuribayashi, M., Yamada, H., Ohmori, T., Yanai, M., and Imoto, T. (1993). Endopeptidase activity of cathepsin C, dipeptidyl aminopeptidase I, from bovine spleen. J. Biochem. 113, 441–449.10.1093/oxfordjournals.jbchem.a124064Search in Google Scholar PubMed
Lange, P.F. and Overall, C.M. (2013). Protein TAILS: when termini tell tales of proteolysis and function. Curr. Opin. Chem. Biol. 17, 73–82.10.1016/j.cbpa.2012.11.025Search in Google Scholar PubMed
Lechtenberg, B.C., Kasperkiewicz, P., Robinson, H., Drag, M., and Riedl, S.J. (2015). The elastase-PK101 structure: mechanism of an ultrasensitive activity-based probe revealed. ACS Chem. Biol. DOI: 10.1021/cb500909n.10.1021/cb500909nSearch in Google Scholar PubMed
Lees, T., Lauffart, B., Hodson, A., Skillen, A., and Mantle, D. (1990). Characterization of aminopeptidases in human kidney and urine. Biochem. Soc. Trans. 18, 666–667.10.1042/bst0180666Search in Google Scholar PubMed
Leiting, B., Pryor, K.D., Wu, J.K., Marsilio, F., Patel, R.A., Craik, C.S., Ellman, J.A., Cummings, R.T., and Thornberry, N.A. (2003). Catalytic properties and inhibition of proline-specific dipeptidyl peptidases II, IV and VII. Biochem. J. 371, 525–532.10.1042/bj20021643Search in Google Scholar PubMed PubMed Central
Li, J., Petrassi, H.M., Tumanut, C., Masick, B.T., Trussell, C., and Harris, J.L. (2009). Substrate optimization for monitoring cathepsin C activity in live cells. Bioorg. Med. Chem. 17, 1064–1070.10.1016/j.bmc.2008.02.002Search in Google Scholar PubMed
Lim, M.D. and Craik, C.S. (2009). Using specificity to strategically target proteases. Bioorg. Med. Chem. 17, 1094–1100.10.1016/j.bmc.2008.03.068Search in Google Scholar PubMed PubMed Central
Lopez-Otin, C. and Overall, C.M. (2002). Protease degradomics: a new challenge for proteomics. Nat. Rev. Mol. Cell Biol. 3, 509–519.10.1038/nrm858Search in Google Scholar PubMed
Maly, D.J., Leonetti, F., Backes, B.J., Dauber, D.S., Harris, J.L., Craik, C.S., and Ellman, J.A. (2002). Expedient solid-phase synthesis of fluorogenic protease substrates using the 7-amino-4-carbamoylmethylcoumarin (ACC) fluorophore. J. Org. Chem. 67, 910–915.10.1021/jo016140oSearch in Google Scholar PubMed
McStay, G.P., Salvesen, G.S., and Green, D.R. (2008). Overlapping cleavage motif selectivity of caspases: implications for analysis of apoptotic pathways. Cell Death Differ. 15, 322–331.10.1038/sj.cdd.4402260Search in Google Scholar PubMed
Ng, N.M., Pike, R.N., and Boyd, S.E. (2009). Subsite cooperativity in protease specificity. Biol. Chem. 390, 401–407.10.1515/BC.2009.065Search in Google Scholar PubMed
Petrassi, H.M., Williams, J.A., Li, J., Tumanut, C., Ek, J., Nakai, T., Masick, B., Backes, B.J., and Harris, J.L. (2005). A strategy to profile prime and non-prime proteolytic substrate specificity. Bioorg. Med. Chem. Lett. 15, 3162–3166.10.1016/j.bmcl.2005.04.019Search in Google Scholar PubMed
Poreba, M. and Drag, M. (2010). Current strategies for probing substrate specificity of proteases. Curr. Med. Chem. 17, 3968–3995.10.2174/092986710793205381Search in Google Scholar PubMed
Poreba, M., Gajda, A., Picha, J., Jiracek, J., Marschner, A., Klein, C.D., Salvesen, G.S., and Drag, M. (2012a). S1 pocket fingerprints of human and bacterial methionine aminopeptidases determined using fluorogenic libraries of substrates and phosphorus based inhibitors. Biochimie 94, 704–710.10.1016/j.biochi.2011.10.014Search in Google Scholar PubMed
Poreba, M., McGowan, S., Skinner-Adams, T.S., Trenholme, K.R., Gardiner, D.L., Whisstock, J.C., To, J., Salvesen, G.S., Dalton, J.P., and Drag, M. (2012b). Fingerprinting the substrate specificity of M1 and M17 aminopeptidases of human malaria, Plasmodium falciparum. PLoS One 7, e31938.10.1371/journal.pone.0031938Search in Google Scholar PubMed PubMed Central
Poreba, M., Kasperkiewicz, P., Snipas, S.J., Fasci, D., Salvesen, G.S., and Drag, M. (2014a). Unnatural amino acids increase sensitivity and provide for the design of highly selective caspase substrates. Cell Death Differ. 21, 1482–1492.10.1038/cdd.2014.64Search in Google Scholar PubMed PubMed Central
Poreba, M., Mihelic, M., Krai, P., Rajkovic, J., Krezel, A., Pawelczak, M., Klemba, M., Turk, D., Turk, B., Latajka, R., et al. (2014b). Unnatural amino acids increase activity and specificity of synthetic substrates for human and malarial cathepsin C. Amino Acids 46, 931–943.10.1007/s00726-013-1654-2Search in Google Scholar PubMed PubMed Central
Prudova, A., auf dem Keller, U., Butler, G.S., and Overall, C.M. (2010). Multiplex N-terminome analysis of MMP-2 and MMP-9 substrate degradomes by iTRAQ-TAILS quantitative proteomics. Mol. Cell. Proteomics 9, 894–911.10.1074/mcp.M000050-MCP201Search in Google Scholar PubMed PubMed Central
Rano, T.A., Timkey, T., Peterson, E.P., Rotonda, J., Nicholson, D.W., Becker, J.W., Chapman, K.T., and Thornberry, N.A. (1997). A combinatorial approach for determining protease specificities: application to interleukin-1β converting enzyme (ICE). Chem. Biol. 4, 149–155.10.1016/S1074-5521(97)90258-1Search in Google Scholar PubMed
Rawlings, N.D., Barrett, A.J., and Bateman, A. (2012). MEROPS: the database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Res. 40, D343–350.10.1093/nar/gkr987Search in Google Scholar PubMed PubMed Central
Sanman, L.E. and Bogyo, M. (2014). Activity-based profiling of proteases. Annu. Rev. Biochem. 83, 249–273.10.1146/annurev-biochem-060713-035352Search in Google Scholar PubMed
Schechter, I. and Berger, A. (1967). On the size of the active site in proteases. I. Papain. Biochem. Biophys. Res. Commun. 27, 157–162.10.1016/S0006-291X(67)80055-XSearch in Google Scholar PubMed
Schilling, O. and Overall, C.M. (2008). Proteome-derived, database-searchable peptide libraries for identifying protease cleavage sites. Nat. Biotechnol. 26, 685–694.10.1038/nbt1408Search in Google Scholar PubMed
Sivaraman, K.K., Oellig, C.A., Huynh, K., Atkinson, S.C., Poreba, M., Perugini, M.A., Trenholme, K.R., Gardiner, D.L., Salvesen, G., Drag, M., et al. (2012). X-ray crystal structure and specificity of the Plasmodium falciparum malaria aminopeptidase PfM18AAP. J. Mol. Biol. 422, 495–507.10.1016/j.jmb.2012.06.006Search in Google Scholar PubMed
Tallan, H.H., Jones, M.E., and Fruton, J.S. (1952). On the proteolytic enzymes of animal tissues. X. Beef spleen cathepsin C. J. Biol. Chem. 194, 793–805.10.1016/S0021-9258(18)55834-8Search in Google Scholar
Taylor, A. (1993). Aminopeptidases: structure and function. FASEB J. 7, 290–298.10.1096/fasebj.7.2.8440407Search in Google Scholar PubMed
Thornberry, N.A., Rano, T.A., Peterson, E.P., Rasper, D.M., Timkey, T., Garcia-Calvo, M., Houtzager, V.M., Nordstrom, P.A., Roy, S., Vaillancourt, J.P., et al. (1997). A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. J. Biol. Chem. 272, 17907–17911.10.1074/jbc.272.29.17907Search in Google Scholar PubMed
Timmer, J.C., Zhu, W., Pop, C., Regan, T., Snipas, S.J., Eroshkin, A.M., Riedl, S.J., and Salvesen, G.S. (2009). Structural and kinetic determinants of protease substrates. Nat. Struct. Mol. Biol. 16, 1101–1108.10.1038/nsmb.1668Search in Google Scholar PubMed PubMed Central
Turk, B. (2006). Targeting proteases: successes, failures and future prospects. Nat. Rev. Drug Discov. 5, 785–799.10.1038/nrd2092Search in Google Scholar PubMed
Turk, B., Turk, D., and Turk, V. (2012). Protease signalling: the cutting edge. EMBO J. 31, 1630–1643.10.1038/emboj.2012.42Search in Google Scholar PubMed PubMed Central
Van Damme, P., Plasman, K., Vandemoortele, G., Jonckheere, V., Maurer-Stroh, S., and Gevaert, K. (2014). Importance of extended protease substrate recognition motifs in steering BNIP-2 cleavage by human and mouse granzymes B. BMC Biochem. 15, 21.10.1186/1471-2091-15-21Search in Google Scholar PubMed PubMed Central
Veillard, F., Potempa, B., Poreba, M., Drag, M., and Potempa, J. (2012). Gingipain aminopeptidase activities in Porphyromonas gingivalis. Biol. Chem. 393, 1471–1476.10.1515/hsz-2012-0222Search in Google Scholar PubMed PubMed Central
Wang, F., Krai, P., Deu, E., Bibb, B., Lauritzen, C., Pedersen, J., Bogyo, M., and Klemba, M. (2011). Biochemical characterization of Plasmodium falciparum dipeptidyl aminopeptidase 1. Mol. Biochem. Parasitol. 175, 10–20.10.1016/j.molbiopara.2010.08.004Search in Google Scholar PubMed PubMed Central
Weglarz-Tomczak, E., Poreba, M., Byzia, A., Berlicki, L., Nocek, B., Mulligan, R., Joachimiak, A., Drag, M., and Mucha, A. (2012). An integrated approach to the ligand binding specificity of Neisseria meningitidis M1 alanine aminopeptidase by fluorogenic substrate profiling, inhibitory studies and molecular modeling. Biochimie 95, 419–428.10.1016/j.biochi.2012.10.018Search in Google Scholar PubMed PubMed Central
Zervoudi, E., Papakyriakou, A., Georgiadou, D., Evnouchidou, I., Gajda, A., Poreba, M., Salvesen, G.S., Drag, M., Hattori, A., Swevers, L., et al. (2011). Probing the S1 specificity pocket of the aminopeptidases that generate antigenic peptides. Biochem. J. 435, 411–420.10.1042/BJ20102049Search in Google Scholar PubMed PubMed Central
©2015 by De Gruyter
Articles in the same Issue
- Frontmatter
- Reviews
- Sortase-mediated backbone cyclization of proteins and peptides
- Making the LINC: SUN and KASH protein interactions
- Enhancers, enhancers – from their discovery to today’s universe of transcription enhancers
- Minireview
- Recent advances and concepts in substrate specificity determination of proteases using tailored libraries of fluorogenic substrates with unnatural amino acids
- Research Articles/Short Communications
- Genes and Nucleic Acids
- microRNA-210 is involved in the regulation of postmenopausal osteoporosis through promotion of VEGF expression and osteoblast differentiation
- Protein Structure and Function
- C-terminal truncation of a Tat passenger protein affects its membrane translocation by interfering with receptor binding
- Aspartate 496 from the subsite S2 drives specificity of human dipeptidyl peptidase III
- Proteolysis
- Evolutionary divergence of Threonine Aspartase1 leads to species-specific substrate recognition
- Purification and characterisation of recombinant His-tagged RgpB gingipain from Porphymonas gingivalis
Articles in the same Issue
- Frontmatter
- Reviews
- Sortase-mediated backbone cyclization of proteins and peptides
- Making the LINC: SUN and KASH protein interactions
- Enhancers, enhancers – from their discovery to today’s universe of transcription enhancers
- Minireview
- Recent advances and concepts in substrate specificity determination of proteases using tailored libraries of fluorogenic substrates with unnatural amino acids
- Research Articles/Short Communications
- Genes and Nucleic Acids
- microRNA-210 is involved in the regulation of postmenopausal osteoporosis through promotion of VEGF expression and osteoblast differentiation
- Protein Structure and Function
- C-terminal truncation of a Tat passenger protein affects its membrane translocation by interfering with receptor binding
- Aspartate 496 from the subsite S2 drives specificity of human dipeptidyl peptidase III
- Proteolysis
- Evolutionary divergence of Threonine Aspartase1 leads to species-specific substrate recognition
- Purification and characterisation of recombinant His-tagged RgpB gingipain from Porphymonas gingivalis