Cysteine proteases: Modes of activation and future prospects as pharmacological targets

Frontiers in Pharmacology

Volumn 7, Issue APR, 2016, Pages

  Verma, Sonia ^a   Dixit, Rajnikant ^a   Pandey, Kailash C ^b  

^a NATIONAL INSTITUTE OF MALARIA RESEARCH   (India)

^b INDIAN COUNCIL OF MEDICAL RESEARCH   (India)

Author keywords

auto catalysis; PH sensor; Prodomain; Protein protein interaction; Trans activation; Zymogen

Indexed keywords

ASPARTIC ACID; ASPARTIC PROTEINASE; CATHEPSIN B; CATHEPSIN F; CATHEPSIN H; CATHEPSIN K; CATHEPSIN L; CATHEPSIN S; CATHEPSIN V; CATHEPSIN W; CATHEPSIN X; CYSTEINE PROTEINASE; DIPEPTIDYL PEPTIDASE I; ENZYME PRECURSOR; EXOPEPTIDASE; HEMOGLOBIN; MEMBRANE PROTEIN; METALLOPROTEINASE; PAPAIN; PROTEINASE; SERINE; SERINE PROTEINASE;

ANTIGEN PRESENTATION; CATALYSIS; DIGESTION; ENZYME INHIBITION; EXTRACELLULAR MATRIX; HUMAN; HYDROLYSIS; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN FOLDING; PROTEIN PROTEIN INTERACTION; REVIEW;

EID: 84967016871     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2016.00107     Document Type: Review

References (76)

1. Almeida, P. C., Nantes, I. L., Rizzi, C. C., Judice, W. A., Chagas, J. R., Juliano, L., et al. (1999). Cysteine proteinase activity regulation. A possible role of heparin and heparin-like glycosaminoglycans. J. Biol. Chem. 274, 30433-30438. doi: 10.1074/jbc.274.43.30433
2. Caglic, D., Pungercar, J. R., Pejler, G., Turk, V., and Turk, B. (2007). Glycosaminoglycans facilitate procathepsin B activation through disruption of propeptide-mature enzyme interactions. J. Biol. Chem. 282, 33076-33085. doi: 10.1074/jbc.M705761200
3. Carmona, E., Dufour, E., Plouffe, C., Takebe, S., Mason, P., Mort, J. S., et al. (1996). Potency and selectivity of the cathepsin L propeptide as an inhibitor of cysteine proteases. Biochemistry 35, 8149-8157. doi: 10.1021/bi952736s
4. Chapman, H. A., Riese, R. J., and Shi, G. P. (1997). Emerging roles for cysteine proteases in human biology. Annu. Rev. Physiol. 59, 63-88. doi: 10.1146/annurev.physiol.59.1.63
5. Collins, P. R., Stack, C. M., O'Neill, S. M., Doyle, S., Ryan, T., Brennan, G. P., et al. (2004). Cathepsin L1, the major protease involved in liver fluke (Fasciola hepatica) virulence: propetide cleavage sites and autoactivation of the zymogen secreted from gastrodermal cells. J. Biol. Chem. 279, 17038-17046. doi: 10.1074/jbc.M308831200
6. Coulombe, R., Grochulski, P., Sivaraman, J., Menard, R., Mort, J. S., and Cygler, M. (1996). Structure of human procathepsin L reveals the molecular basis of inhibition by the prosegment. EMBO J. 15, 5492-5503
7. Cuozzo, J. W., Tao, K., Wu, Q. L., Young, W., and Sahagian, G. G. (1995). Lysine-based structure in the proregion of procathepsin L is the recognition site for mannose phosphorylation. J. Biol. Chem. 270, 15611-15619. doi: 10.1074/jbc.270.26.15611
8. Cygler, M., Sivaraman, J., Grochulski, P., Coulombe, R., Storer, A. C., and Mort, J. S. (1996). Structure of rat procathepsin B: model for inhibition of cysteine protease activity by the proregion. Structure 4, 405-416. doi: 10.1016/S0969-2126(96)00046-9
9. Dahl, S. W., Halkier, T., Lauritzen, C., Dolenc, I., Pedersen, J., Turk, V., et al. (2001). Human recombinant pro-dipeptidyl peptidase I (cathepsin C) can be activated by cathepsins L and S but not by autocatalytic processing. Biochemistry 40, 1671-1678. doi: 10.1021/bi001693z
10. Dalton, J. P., and Brindley, P. J. (1996). Schistosome asparaginyl endopeptidase SM32 in hemoglobin digestion. Parasitol Today 12:125. doi: 10.1016/0169-4758(96)80676-4
11. Dalton, J. P., Brindley, P. J., Donnelly, S., and Robinson, M. W. (2009). The enigmatic asparaginyl endopeptidase of helminth parasites. Trends Parasitol. 25, 59-61. doi: 10.1016/j.pt.2008.11.002
12. Dalton, J. P., Clough, K. A., Jones, M. K., and Brindley, P. J. (1997). The cysteine proteinases of Schistosoma mansoni cercariae. Parasitology 114, 105-112. doi: 10.1017/S003118209600830X
13. Dalton, J. P., and Dvorak, J. (2014). Activating the cathepsin B1 of a parasite: a major route with alternative pathways? Structure 22, 1696-1698. doi: 10.1016/j.str.2014.11.003
14. Dieter Bromme, S. W. (2011). "Role of cysteine cathepsins in extracellular proteolysis," in Extracellular Matrix Degradation, eds R. P. M. William and C. Parks (Berlin: Springer), 23-51
15. Feliciangeli, S. F., Thomas, L., Scott, G. K., Subbian, E., Hung, C. H., Molloy, S. S., et al. (2006). Identification of a pH sensor in the furin propeptide that regulates enzyme activation. J. Biol. Chem. 281, 16108-16116. doi: 10.1074/jbc.M600760200
16. Francis, S. E., Sullivan, D. J. Jr., and Goldberg, D. E. (1997). Hemoglobin metabolism in the malaria parasite Plasmodium falciparum. Annu. Rev. Microbiol. 51, 97-123. doi: 10.1146/annurev.micro.51.1.97
17. Gills, J. J., Lopiccolo, J., Tsurutani, J., Shoemaker, R. H., Best, C. J., Abu-Asab, M. S., et al. (2007). Nelfinavir, A lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo. Clin. Cancer Res. 13, 5183-5194. doi: 10.1158/1078-0432.CCR-07-0161
18. Gotz, B., and Klinkert, M. Q. (1993). Expression and partial characterization of a cathepsin B-like enzyme (Sm31) and a proposed 'haemoglobinase' (Sm32) from Schistosoma mansoni. Biochem. J. 290(Pt 3), 801-806. doi: 10.1042/bj2900801
19. Groves, M. R., Coulombe, R., Jenkins, J., and Cygler, M. (1998). Structural basis for specificity of papain-like cysteine protease proregions toward their cognate enzymes. Proteins 32, 504-514. doi: 10.1002/(SICI)1097-0134(19980901)32:4<504::AID-PROT8>3.0.CO;2-F
20. Hasilik, A., Wrocklage, C., and Schroder, B. (2009). Intracellular trafficking of lysosomal proteins and lysosomes. Int. J. Clin. Pharmacol. Ther. 47(Suppl. 1), S18-S33
21. Hirai, T., Kanda, T., Sato, K., Takaishi, M., Nakajima, K., Yamamoto, M., et al. (2013). Cathepsin K is involved in development of psoriasis-like skin lesions through TLR-dependent Th17 activation. J. Immunol. 190, 4805-4811. doi: 10.4049/jimmunol.1200901
22. Kay, J., and Kassell, B. (1971). The autoactivation of trypsinogen. J. Biol. Chem. 246, 6661-6665
23. Khan, A. R., and James, M. N. (1998). Molecular mechanisms for the conversion of zymogens to active proteolytic enzymes. Protein Sci. 7, 815-836. doi: 10.1002/pro.5560070401
24. Laurent-Matha, V., Derocq, D., Prebois, C., Katunuma, N., and Liaudet-Coopman, E. (2006). Processing of human cathepsin D is independent of its catalytic function and auto-activation: involvement of cathepsins L and B. J. Biochem. 139, 363-371. doi: 10.1093/jb/mvj037
25. Lecaille, F., Kaleta, J., and Bromme, D. (2002). Human and parasitic papain-like cysteine proteases: their role in physiology and pathology and recent developments in inhibitor design. Chem. Rev. 102, 4459-4488. doi: 10.1021/cr0101656
26. Li, Z., Hou, W. S., and Bromme, D. (2000). Collagenolytic activity of cathepsin K is specifically modulated by cartilage-resident chondroitin sulfates. Biochemistry 39, 529-536. doi: 10.1021/bi992251u
27. Li, Z., Kienetz, M., Cherney, M. M., James, M. N., and Bromme, D. (2008). The crystal and molecular structures of a cathepsin K:chondroitin sulfate complex. J. Mol. Biol. 383, 78-91. doi: 10.1016/j.jmb.2008.07.038
28. Lowther, J., Robinson, M. W., Donnelly, S. M., Xu, W., Stack, C. M., Matthews, J. M., et al. (2009). The importance of pH in regulating the function of the Fasciola hepatica cathepsin L1 cysteine protease. PLoS Negl. Trop. Dis. 3:e369. doi: 10.1371/journal.pntd.0000369
29. Mach, L., Mort, J. S., and Glossl, J. (1994). Maturation of human procathepsin B. Proenzyme activation and proteolytic processing of the precursor to the mature proteinase, in vitro, are primarily unimolecular processes. J. Biol. Chem. 269, 13030-13035
30. Martinez, M., and Diaz, I. (2008). The origin and evolution of plant cystatins and their target cysteine proteinases indicate a complex functional relationship. BMC Evol. Biol. 8:198. doi: 10.1186/1471-2148-8-198
31. Mason, R. W., and Massey, S. D. (1992). Surface activation of pro-cathepsin L. Biochem. Biophys. Res. Commun. 189, 1659-1666. doi: 10.1016/0006-291X(92)90268-P
32. McGrath, M. E. (1999). The lysosomal cysteine proteases. Annu. Rev. Biophys. Biomol. Struct. 28, 181-204. doi: 10.1146/annurev.biophys.28.1.181
33. McQueney, M. S., Amegadzie, B. Y., D'Alessio, K., Hanning, C. R., McLaughlin, M. M., McNulty, D., et al. (1997). Autocatalytic activation of human cathepsin K. J. Biol. Chem. 272, 13955-13960. doi: 10.1074/jbc.272.21.13955
34. Menard, R., Carmona, E., Takebe, S., Dufour, E., Plouffe, C., Mason, P., et al. (1998). Autocatalytic processing of recombinant human procathepsin L. Contribution of both intermolecular and unimolecular events in the processing of procathepsin L in vitro. J. Biol. Chem. 273, 4478-4484. doi: 10.1074/jbc.273.8.4478
35. Mullard, A. (2012). Protein-protein interaction inhibitors get into the groove. Nat. Rev. Drug Discov. 11, 173-175. doi: 10.1038/nrd3680
36. Nagler, D. K., and Menard, R. (1998). Human cathepsin X: a novel cysteine protease of the papain family with a very short proregion and unique insertions. FEBS Lett. 434, 135-139. doi: 10.1016/S0014-5793(98)00964-8
37. Nishimura, Y., Kawabata, T., Furuno, K., and Kato, K. (1989). Evidence that aspartic proteinase is involved in the proteolytic processing event of procathepsin L in lysosomes. Arch. Biochem. Biophys. 271, 400-406. doi: 10.1016/0003-9861(89)90289-0
38. Novinec, M., Kovacic, L., Lenarcic, B., and Baici, A. (2010). Conformational flexibility and allosteric regulation of cathepsin K. Biochem. J. 429, 379-389. doi: 10.1042/BJ20100337
39. Novinec, M., Lenarcic, B., and Turk, B. (2014). Cysteine cathepsin activity regulation by glycosaminoglycans. Biomed. Res. Int. 2014:309718. doi: 10.1155/2014/309718
40. Pandey, K. C. (2013). "Cysteine proteases of human malaria parasites," in Proteases in Health and Disease, eds S. Chakraborti and N. S. Dhalla (Berlin: springer), 121-134
41. Pandey, K. C., Barkan, D. T., Sali, A., and Rosenthal, P. J. (2009). Regulatory elements within the prodomain of Falcipain-2, a cysteine protease of the malaria parasite Plasmodium falciparum. PLoS ONE 4:e5694. doi: 10.1371/journal.pone.0005694
42. Pandey, K. C., and Dixit, R. (2012). Structure-function of falcipains: malarial cysteine proteases. J. Trop. Med. 2012:345195. doi: 10.1155/2012/345195
43. Pandey, K. C., Sijwali, P. S., Singh, A., Na, B. K., and Rosenthal, P. J. (2004). Independent intramolecular mediators of folding, activity, and inhibition for the Plasmodium falciparum cysteine protease falcipain-2. J. Biol. Chem. 279, 3484-3491. doi: 10.1074/jbc.M310536200
44. Pandey, K. C., Wang, S. X., Sijwali, P. S., Lau, A. L., McKerrow, J. H., and Rosenthal, P. J. (2005). The Plasmodium falciparum cysteine protease falcipain-2 captures its substrate, hemoglobin, via a unique motif. Proc. Natl. Acad. Sci. U.S.A. 102, 9138-9143. doi: 10.1073/pnas.0502368102
45. Petrov, V., Fagard, R., and Lijnen, P. (2000). Effect of protease inhibitors on angiotensin-converting enzyme activity in human T-lymphocytes. Am. J. Hypertens. 13, 535-539. doi: 10.1016/S0895-7061(99)00236-8
46. Pungercar, J. R., Caglic, D., Sajid, M., Dolinar, M., Vasiljeva, O., Pozgan, U., et al. (2009). Autocatalytic processing of procathepsin B is triggered by proenzyme activity. FEBS J 276, 660-668. doi: 10.1111/j.1742-4658.2008.06815.x
47. Rosenthal, P. J. (2011). Falcipains and other cysteine proteases of malaria parasites. Adv. Exp. Med. Biol. 712, 30-48. doi: 10.1007/978-1-4419-8414-2_3
48. Rosenthal, P. J., Sijwali, P. S., Singh, A., and Shenai, B. R. (2002). Cysteine proteases of malaria parasites: targets for chemotherapy. Curr. Pharm. Des. 8, 1659-1672. doi: 10.2174/1381612023394197
49. Rossi, A., Deveraux, Q., Turk, B., and Sali, A. (2004). Comprehensive search for cysteine cathepsins in the human genome. Biol. Chem. 385, 363-372. doi: 10.1515/BC.2004.040
50. Rowan, A. D., Mason, P., Mach, L., and Mort, J. S. (1992). Rat procathepsin B. Proteolytic processing to the mature form in vitro. J. Biol. Chem. 267, 15993-15999
51. Rozman, J., Stojan, J., Kuhelj, R., Turk, V., and Turk, B. (1999). Autocatalytic processing of recombinant human procathepsin B is a bimolecular process. FEBS Lett. 459, 358-362. doi: 10.1016/S0014-5793(99)01302-2
52. Sage, J., Mallevre, F., Barbarin-Costes, F., Samsonov, S. A., Gehrcke, J. P., Pisabarro, M. T., et al. (2013). Binding of chondroitin 4-sulfate to cathepsin S regulates its enzymatic activity. Biochemistry 52, 6487-6498. doi: 10.1021/bi400925g
53. Sajid, M., and McKerrow, J. H. (2002). Cysteine proteases of parasitic organisms. Mol. Biochem. Parasitol. 120, 1-21. doi: 10.1016/S0166-6851(01)00438-8
54. Sajid, M., McKerrow, J. H., Hansell, E., Mathieu, M. A., Lucas, K. D., Hsieh, I., et al. (2003). Functional expression and characterization of Schistosoma mansoni cathepsin B and its trans-activation by an endogenous asparaginyl endopeptidase. Mol. Biochem. Parasitol. 131, 65-75. doi: 10.1016/S0166-6851(03)00194-4
55. Salminen-Mankonen, H. J., Morko, J., and Vuorio, E. (2007). Role of cathepsin K in normal joints and in the development of arthritis. Curr. Drug Targets 8, 315-323. doi: 10.2174/138945007779940188
56. Schroder, B. A., Wrocklage, C., Hasilik, A., and Saftig, P. (2010). The proteome of lysosomes. Proteomics 10, 4053-4076. doi: 10.1002/pmic.201000196
57. Shahian, T., Lee, G. M., Lazic, A., Arnold, L. A., Velusamy, P., Roels, C. M., et al. (2009). Inhibition of a viral enzyme by a small-molecule dimer disruptor. Nat. Chem. Biol. 5, 640-646. doi: 10.1038/nchembio.192
58. Sijwali, P. S., Koo, J., Singh, N., and Rosenthal, P. J. (2006). Gene disruptions demonstrate independent roles for the four falcipain cysteine proteases of Plasmodium falciparum. Mol. Biochem. Parasitol. 150, 96-106. doi: 10.1016/j.molbiopara.2006.06.013
59. Sijwali, P. S., and Rosenthal, P. J. (2004). Gene disruption confirms a critical role for the cysteine protease falcipain-2 in hemoglobin hydrolysis by Plasmodium falciparum. Proc. Natl. Acad. Sci. U.S.A. 101, 4384-4389. doi: 10.1073/pnas.0307720101
60. Sijwali, P. S., Shenai, B. R., and Rosenthal, P. J. (2002). Folding of the Plasmodium falciparum cysteine protease falcipain-2 is mediated by a chaperone-like peptide and not the prodomain. J. Biol. Chem. 277, 14910-14915. doi: 10.1074/jbc.M109680200
61. Sivaraman, J., Lalumiere, M., Menard, R., and Cygler, M. (1999). Crystal structure of wild-type human procathepsin K. Protein Sci. 8, 283-290. doi: 10.1110/ps.8.2.283
62. Sivaraman, J., Nagler, D. K., Zhang, R., Menard, R., and Cygler, M. (2000). Crystal structure of human procathepsin X: a cysteine protease with the proregion covalently linked to the active site cysteine. J. Mol. Biol. 295, 939-951. doi: 10.1006/jmbi.1999.3410
63. Sripa, J., Laha, T., To, J., Brindley, P. J., Sripa, B., Kaewkes, S., et al. (2010). Secreted cysteine proteases of the carcinogenic liver fluke, Opisthorchis viverrini: regulation of cathepsin F activation by autocatalysis and trans-processing by cathepsin B. Cell Microbiol. 12, 781-795. doi: 10.1111/j.1462-5822.2010.01433.x
64. Stack, C. M., Caffrey, C. R., Donnelly, S. M., Seshaadri, A., Lowther, J., Tort, J. F., et al. (2008). Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepatica. J. Biol. Chem. 283, 9896-9908. doi: 10.1074/jbc.M708521200
65. Subramanian, S., Hardt, M., Choe, Y., Niles, R. K., Johansen, E. B., Legac, J., et al. (2009). Hemoglobin cleavage site-specificity of the Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3. PLoS ONE 4:e5156. doi: 10.1371/journal.pone.0005156
66. Subramanian, S., Sijwali, P. S., and Rosenthal, P. J. (2007). Falcipain cysteine proteases require bipartite motifs for trafficking to the Plasmodium falciparum food vacuole. J. Biol. Chem. 282, 24961-24969. doi: 10.1074/jbc.M703316200
67. Sundararaj, S., Singh, D., Saxena, A. K., Vashisht, K., Sijwali, P. S., Dixit, R., et al. (2012). The ionic and hydrophobic interactions are required for the auto activation of cysteine proteases of Plasmodium falciparum. PLoS ONE 7:e47227. doi: 10.1371/journal.pone.0047227
68. Tao, K., Stearns, N. A., Dong, J., Wu, Q. L., and Sahagian, G. G. (1994). The proregion of cathepsin L is required for proper folding, stability, and ER exit. Arch. Biochem. Biophys. 311, 19-27. doi: 10.1006/abbi.1994.1203
69. Turk, D., Podobnik, M., Kuhelj, R., Dolinar, M., and Turk, V. (1996). Crystal structures of human procathepsin B at 3.2 and 3.3 Angstroms resolution reveal an interaction motif between a papain-like cysteine protease and its propeptide. FEBS Lett. 384, 211-214. doi: 10.1016/0014-5793(96)00309-2
70. Turk, V., Stoka, V., Vasiljeva, O., Renko, M., Sun, T., Turk, B., et al. (2012). Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochim. Biophys. Acta 1824, 68-88. doi: 10.1016/j.bbapap.2011.10.002
71. Vasiljeva, O., Dolinar, M., Pungercar, J. R., Turk, V., and Turk, B. (2005). Recombinant human procathepsin S is capable of autocatalytic processing at neutral pH in the presence of glycosaminoglycans. FEBS Lett. 579, 1285-1290. doi: 10.1016/j.febslet.2004.12.093
72. Vasiljeva, O., Reinheckel, T., Peters, C., Turk, D., Turk, V., and Turk, B. (2007). Emerging roles of cysteine cathepsins in disease and their potential as drug targets. Curr. Pharm. Des. 13, 387-403. doi: 10.2174/138161207779313542
73. Vernet, T., Berti, P. J., de Montigny, C., Musil, R., Tessier, D. C., Menard, R., et al. (1995). Processing of the papain precursor. The ionization state of a conserved amino acid motif within the Pro region participates in the regulation of intramolecular processing. J. Biol. Chem. 270, 10838-10846
74. Walsh, G. (2014). "Protein sources," in Proteins: Biochemistry and Biotechnology, 2nd Edn (Hoboken, NJ: Wiley-Blackwell), 80-83. doi: 10.1002/9781119117599.ch3
75. Williamson, D. M., Elferich, J., Ramakrishnan, P., Thomas, G., and Shinde, U. (2013). The mechanism by which a propeptide-encoded pH sensor regulates spatiotemporal activation of furin. J. Biol. Chem. 288, 19154-19165. doi: 10.1074/jbc.M112.442681
76. Willstätter, R., and Bamann, E. (1929). über die proteasen der magenschleimhaut. Erste abhandlung über die enzyme der leukocyten. Hoppe-Seyler's Z. Physiol. Chem. 180, 127-143. doi: 10.1515/bchm2.1929.180.1-3.127