Parasite cysteine proteinases

Summary

Cysteine proteinases of protozoan and helminth parasites are considered to have a high potential as targets for novel antiparasite agents. This has stimulated research on the enzymes and a large body of data has now been accumulated. This Perspective provides an overview of the current situation, with recent advances being highlighted. Emphasis is given to the Type I cysteine proteinases of trypanosomatid protozoa, which are atypical in having an extra C-terminal domain, and the asparaginyl endopeptidase ofSchistosoma, for which the only homologues known are those in plants. The locations of parasite cysteine proteinases are described, with emphasis on the extralysosomal sites, and the putative roles of the enzymes in host-parasite interactions, including parasite nutrition and host invasion, are discussed. The major advances being made in elucidating cysteine proteinase function in protozoan parasites through genetic manipulation, including targeted gene deletion, are presented, with the Type I cysteine proteinases ofLeishmania being used as an example. The importance of this approach in the validation of the enzymes as drug targets is discussed. The current status of attempts to exploit parasite cysteine proteinases with drugs is presented, and future prospects are outlined.

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References

  1. 1

    North, M.J., Mottram, J.C. and Coombs, G.H., Parasitol. Today, 6 (1990) 270.

    Google Scholar 

  2. 2

    McKerrow, J.H., Sun, E., Rosenthal, P.J. and Bouvier, J., Annu. Rev. Microbiol., 47 (1993) 821.

    Google Scholar 

  3. 3

    Coombs, G.H. and Mottram, J.C., In Hide, G., Mottram, J.C., Coombs, G.H. and Holmes, P.H. (Eds.) Trypanosomiasis and Leishmaniasis: Biology and Control, CAB International, Oxford, U.K., 1996, pp. 177–197.

    Google Scholar 

  4. 4

    Protease Inhibition as a Target for Parasite Chemotherapy, WHO TDR, San Francisco, 1995.

  5. 5

    McKerrow, J.H., Perspect. Drug Discov. Design, 2 (1994) 437.

    Google Scholar 

  6. 6

    Mallinson, D.J., Livingstone, J., Appleton, K.M., Lees, S.J., Coombs, G.H. and North, M.J., Microbiology, 141 (1995) 3077.

    Google Scholar 

  7. 7

    Mallinson, D.J., Lockwood, B.C., Coombs, G.H. and North, M.J., J. Gen. Microbiol. 140, (1994) 2725.

    Google Scholar 

  8. 8

    Provenzano, D. and Alderete, J.F., Infect. Immun., 63 (1995) 3388.

    Google Scholar 

  9. 9

    Keene, W.E., Petitt, M.G., Allen, S. and McKerrow, J.H., J. Exp. Med., 163 (1986) 536.

    Google Scholar 

  10. 10

    Schulte, W. and Scholze, H., J. Protozool., 36 (1989) 538.

    Google Scholar 

  11. 11

    Nesterenko, M.V., Tilley, M. and Upton, S.J., Microbios, 83 (1995) 77.

    Google Scholar 

  12. 12

    Michalski, W.P., Crooks, J.K. and Prowse, S.J., Int. J. Parasitol., 24 (1994) 189.

    Google Scholar 

  13. 13

    Choi, W.-Y., Nam, H.-W. and Youn, J.-H., Korean J. Parasitol., 27 (1989) 161.

    Google Scholar 

  14. 14

    Aldape, K., Huizinga, H., Bouvier, J. and McKerrow, J., Exp. Parasitol., 78 (1994) 230.

    Google Scholar 

  15. 15

    Liu, D.W., Kato, H., Nakamura, T. and Sugane, K., Mol. Biochem. Parasitol., 76 (1996) 11.

    Google Scholar 

  16. 16

    Todorova, V.K., Knox, D.P. and Kennedy, M.W., Parasitology, 111 (1995) 201.

    Google Scholar 

  17. 17

    Dowd, A.J., McGonigle, S. and Dalton, J.P., Eur. J. Biochem., 232 (1995) 241.

    Google Scholar 

  18. 18

    Brown, A., Burleigh, J.M., Billett, E.E. and Pritchard, D.I., Parasitology, 110 (1995) 555.

    Google Scholar 

  19. 19

    Maki, J. and Yanagisawa, T.J., Helminth, 60 (1986) 31.

    Google Scholar 

  20. 20

    Cox, G.N., Pratt, D., Hageman, R. and Boisvenue, R.J., Mol. Biochem. Parasitol., 41 (1990) 25.

    Google Scholar 

  21. 21

    Cazzulo, J.J., Couso, R., Raimondi, A., Wernstedt, C. and Hellman, U., Mol. Biochem. Parasitol., 33 (1989) 33.

    Google Scholar 

  22. 22

    Robertson, C.D. and Coombs, G.H., Mol. Biochem. Parasitol., 42 (1990) 269.

    Google Scholar 

  23. 23

    Robertson, C.D. and Coombs, G.H., Microbiology, 140 (1994) 417.

    Google Scholar 

  24. 24

    Harth, G., Andrews, N., Mills, A.A., Engel, J.C., Smith, R. and McKerrow, J.H., Mol. Biochem. Parasitol., 58 (1993) 17.

    Google Scholar 

  25. 25

    Meirelles, M.N.L., Juliano, L., Carmona, E., Silva, S.G., Costa, E.M., Murta, A.C.M. and Scharfstein, J., Mol. Biochem. Parasitol., 52 (1992) 175.

    Google Scholar 

  26. 26

    Franke de Cazzulo, B.M., Martínez, J., North, M.J., Coombs, G.H. and Cazzulo, J.J., FEMS Microbiol. Lett., 124 (1994) 81.

    Google Scholar 

  27. 27

    Eakin, A.E., Mills, A.A., Harth, G., McKerrow, J.H. and Craik, C.S., J. Biol. Chem., 267 (1992) 7411.

    Google Scholar 

  28. 28

    Campetella, O., Henriksson, J., Aslund, L., Frasch, A.C.C., Pettersson, U. and Cazzulo, J.J., Mol. Biochem. Parasitol., 50 (1992) 225.

    Google Scholar 

  29. 29

    Mottram, J.C., Souza, A.E., Hutchison, J.E., Carter, R., Frame, M.J. and Coombs, G.H., Proc. Natl. Acad. Sci. USA, 93 (1996) 6008.

    Google Scholar 

  30. 30

    Souza, A.E., Waugh, S., Coombs, G.H. and Mottram, J.C., FEBS Lett., 311 (1992) 124.

    Google Scholar 

  31. 31

    Mottram, J.C., North, M.J., Barry, J.D. and Coombs, G.H., FEBS Lett., 258 (1989) 211.

    Google Scholar 

  32. 32

    Parodi, A.J., Labriola, C. and Cazzulo, J.J., Mol. Biochem. Parasitol., 69 (1995) 247.

    Google Scholar 

  33. 33

    Labriola, C., Cazzulo, J.J. and Parodi, A.J., J. Cell Biol., 130 (1995) 771.

    Google Scholar 

  34. 34

    Martinez, J., Campetella, O., Frasch, A.C.C. and Cazzulo, J.J., Immunol. Lett., 35 (1993) 191.

    Google Scholar 

  35. 35

    Pamer, E.G., Davis, C.E. and So, M., Infect. Immun., 59 (1991) 1074.

    Google Scholar 

  36. 36

    Eakin, A.E., McGrath, M.E., McKerrow, J.H., Fletterick, R.J. and Craik, C.S., J. Biol. Chem., 268 (1993) 6115.

    Google Scholar 

  37. 37

    Duboise, S.M., Vannier-Santos, M.A., Costa-Pinto, D., Rivas, L., Pan, A.A., Traub-Cseko, Y.M., de Souza, W. and McMahon-Pratt, D., Mol. Biochem. Parasitol., 68 (1994) 119.

    Google Scholar 

  38. 38

    North, M.J., Parasitol. Today, 7 (1991) 249.

    Google Scholar 

  39. 39

    Lima, A.P.C.A., Tessier, D.C., Thomas, D.Y., Scharfstein, J., Storer, A.C. and Vernet, T., Mol. Biochem. Parasitol., 67 (1994) 333.

    Google Scholar 

  40. 40

    Mottram, J.C., Robertson, C.D., Coombs, G.H. and Barry, J.D., Mol. Microbiol., 6 (1992) 1925.

    Google Scholar 

  41. 41

    Traub-Cseko, Y.M., Duboise, M., Boukai, L.K. and McMahon-Pratt, D., Mol. Biochem. Parasitol., 57 (1993) 101.

    Google Scholar 

  42. 42

    Bart, G., Coombs, G.H. and Mottram, J.C., Mol. Biochem. Parasitol., 73 (1995) 271.

    Google Scholar 

  43. 43

    Robertson, C.D. and Coombs, G.H., Mol. Biochem. Parasitol., 62 (1993) 271.

    Google Scholar 

  44. 44

    Davis, A.H., Nanduri, J. and Watson, D.C., J. Biol. Chem., 262 (1987) 12851.

    Google Scholar 

  45. 45

    Ishii, S., Methods Enzymol., 244 (1994) 604.

    Google Scholar 

  46. 46

    Gotz, B. and Klinkert, M.Q., Biochem. J., 290 (1993) 801.

    Google Scholar 

  47. 47

    Takeda, O., Miura, Y., Mitta, M., Matsushita, H., Kato, I., Abe, Y., Yokosawa, H. and Ishii, S., J. Biochem., 116 (1994) 541.

    Google Scholar 

  48. 48

    Becker, C., Shutov, A.D., Nong, V.H., Senyuk, V.I., Jung, R., Horstmann, C., Fischer, J., Nielsen, N.C. and Muntz, K., Eur. J. Biochem., 228 (1995) 456.

    Google Scholar 

  49. 49

    Dalton, J.P., Hola-Jamriska, L. and Brindley, P.J., Parasitology, 111 (1995) 575.

    Google Scholar 

  50. 50

    Hara-Nishimura, I., Shimada, T., Hiraiwa, N. and Nishimura, M., J. Plant Physiol., 145 (1995) 632.

    Google Scholar 

  51. 51

    Dalton, J.P. and Brindley, P.J., Parasitol. Today, 12 (1996) 125.

    Google Scholar 

  52. 52

    Lawrence, J.D., J. Parasitol., 59 (1973) 60.

    Google Scholar 

  53. 53

    Zussman, R.A., Bauman, P.M. and Petruska, J.C., J. Parasitol., 56 (1970) 75.

    Google Scholar 

  54. 54

    Dresden, M.H. and Deelder, A.M., Exp. Parasitol., 48 (1979) 190.

    Google Scholar 

  55. 55

    Smith, A.M., Dalton, J.P., Clough, K.A., Kilbane, C.L., Harrop, S.A., Hole, N. and Brindley, P.J., Mol. Biochem. Parasitol., 67 (1994) 11.

    Google Scholar 

  56. 56

    Becker, M.M., Harrop, S.A., Dalton, J.P., Kalinna, B.H., McManus, D.P. and Brindley, P.J., J. Biol. Chem., 270 (1995) 24496.

    Google Scholar 

  57. 57

    Butler, R., Michel, A., Kunz, W. and Klinkert, M.Q., Protein Pept. Lett., 2 (1995) 313.

    Google Scholar 

  58. 58

    Bontempi, E., Martinez, J. and Cazzulo, J.J., Mol. Biochem. Parasitol., 33 (1989) 43.

    Google Scholar 

  59. 59

    Souto-Padron, T., Campetella, O.E., Cazzulo, J.J. and de Souza, W., J. Cell Sci., 96 (1990) 485.

    Google Scholar 

  60. 60

    Mbawa, Z.R., Webster, P. and Lonsdale-Eccles, J.D., Eur. J. Cell Biol., 56 (1991) 243.

    Google Scholar 

  61. 61

    Rosenthal, P.J., McKerrow, J.H., Aikawa, M., Nagasawa, H. and Leech, J.H., J. Clin. Invest., 82 (1988) 1560.

    Google Scholar 

  62. 62

    Ostoa-Saloma, P., Cabrera, N., Becker, I. and Perez-Montfort, R., Mol. Biochem. Parasitol., 32 (1989) 133.

    Google Scholar 

  63. 63

    Lockwood, B.C., North, M.J. and Coombs, G.H., Mol. Biochem. Parasitol., 30 (1988) 135.

    Google Scholar 

  64. 64

    Parenti, D.M., J. Infect. Dis., 160 (1989) 1076.

    Google Scholar 

  65. 65

    Pupkis, M.F., Tetley, L. and Coombs, G.H., Exp. Parasitol., 62 (1986) 29.

    Google Scholar 

  66. 66

    Pupkis, M.F. and Coombs, G.H., J. Gen. Microbiol., 130 (1984) 2375.

    Google Scholar 

  67. 67

    Murta, A.C.M., Persechini, P.M., Padron, T.D., de Souza, W., Guimaraes, J.A. and Scharfstein, J., Mol. Biochem. Parasitol., 43 (1990) 27.

    Google Scholar 

  68. 68

    McGrath, M.E., Eakin, A.E., Engel, J.C., McKerrow, J.H., Craik, C.S. and Fletterick, R.J., J. Mol. Biol., 247 (1995) 251.

    Google Scholar 

  69. 69

    Arnholdt, A.C.V., Piuvezam, M.R., Russo, D.M., Lima, A.P.C.A., Pedrosa, R.C., Reed, S.G. and Scharfstein, J., J. Immunol., 151 (1993) 3171.

    Google Scholar 

  70. 70

    Fresno, M., Hernandezmunain, C., Dediego, J., Rivas, L., Scharfstein, J. and Bonay, P., Braz. J. Med. Biol. Res., 27 (1994) 431.

    Google Scholar 

  71. 71

    Yokoyama-Yasunaka, J.K.U., Pral, E.M.F., Oliveira, O.C., Alfieri, S.C. and Stolf, A.M.S., Acta Trop., 57 (1994) 307.

    Google Scholar 

  72. 72

    Ilg, T., Fuchs, M., Gnau, V., Wolfram, M., Harbecke, D. and Overath, P., Mol. Biochem. Parasitol., 67 (1994) 193.

    Google Scholar 

  73. 73

    Leippe, M., Sievertsen, H.J., Tannich, E. and Horstmann, R.D., Parasitology, 111 (1995) 569.

    Google Scholar 

  74. 74

    Bozner, P. and Demes, P., Parasitology, 102 (1991) 113.

    Google Scholar 

  75. 75

    Garber, G.E. and Lemchuk-Favel, L.T., Can. J. Microbiol., 35 (1989) 903.

    Google Scholar 

  76. 76

    North, M.J., Robertson, C.D. and Coombs, G.H., Mol. Biochem. Parasitol., 39 (1990) 183.

    Google Scholar 

  77. 77

    Luaces, A.L. and Barrett, A.J., Biochem. J., 250 (1988) 903.

    Google Scholar 

  78. 78

    Reed, S., Bouvier, J., Pollack, A.S., Engel, J.C., Brown, M., Hirata, K., Que, X.C., Eakin, A., Hagblom, P., Gillin, F. and McKerrow, J.H., J. Clin. Invest., 91 (1993) 1532.

    Google Scholar 

  79. 79

    Tannich, E., Scholze, H., Nickel, R. and Horstmann, R.D., J. Biol. Chem., 266 (1991) 4798.

    Google Scholar 

  80. 80

    Alderete, J.F., Newton, E., Dennis, C. and Neale, K.A., Genitourin. Med., 67 (1991) 331.

    Google Scholar 

  81. 81

    Bozner, P., Gombosova, A., Valent, M., Demes, P. and Alderete, J.F., Parasitology, 105 (1992) 387.

    Google Scholar 

  82. 82

    Garber, G.E. and Lemchukfavel, L.T., Parasitol. Res., 80 (1994) 361.

    Google Scholar 

  83. 83

    Scott, D.A., North, M.J. and Coombs, G.H., Int. J. Parasitol., 25 (1995) 657.

    Google Scholar 

  84. 84

    Scott, D.A., North, M.J. and Coombs, G.H., Exp. Parasitol., 80 (1995) 345.

    Google Scholar 

  85. 85

    Keene, W.E., Hidalgo, M.E., Orozco, E. and McKerrow, J.H., Exp. Parasitol., 71 (1990) 199.

    Google Scholar 

  86. 86

    Navarro-Garcia, F., Chavez-Duenas, L., Tsutsumi, V., Delrio, F.P. and Lopez-Revilla, R., Exp. Parasitol., 80 (1995) 361.

    Google Scholar 

  87. 87

    Perez-Tamayo, R., Becker, I., Montfort, I., Ostoa-Saloma, P. and Perez-Montfort, R., Parasitol. Res., 77 (1991) 192.

    Google Scholar 

  88. 88

    Reed, S.L., Keene, W.E. and McKerrow, J.H., J. Clin. Microbiol., 27 (1989) 2772.

    Google Scholar 

  89. 89

    Montfort, I., Pereztamayo, R., Canto, A.G., Deleon, M.D.G., Olivos, A. and Tello, E., J. Parasitol., 79 (1993) 98.

    Google Scholar 

  90. 90

    Bruchhaus, I. and Tannich, E., Parasitol. Res., 82 (1996) 189.

    Google Scholar 

  91. 91

    Arroyo, R. and Alderete, J.F., Infect. Immun., 57 (1989) 2991.

    Google Scholar 

  92. 92

    Avila, E.E. and Calderon, J., Exp. Parasitol., 76 (1993) 232.

    Google Scholar 

  93. 93

    Mitro, K., Bhagavathiammai, A., Zhou, O.M., Bobbett, G., McKerrow, J.H., Chokshi, R., Chokshi, B. and James, E.R., Exp. Parasitol., 78 (1994) 377.

    Google Scholar 

  94. 94

    Kamata, I., Yamada, M., Uchikawa, R., Matsuda, S. and Arizono, N., Clin. Exp. Immunol., 102 (1995) 71.

    Google Scholar 

  95. 95

    Gao, C.Y. and Zelenka, P.S., Exp. Cell Res., 219 (1995) 612.

    Google Scholar 

  96. 96

    Authié, E., Duvallet, G., Robertson, C. and Williams, D.J.L., Parasite Immunol., 15 (1993) 465.

    Google Scholar 

  97. 97

    Dalton, J.P., Smith, A.M., Clough, K.A. and Brindley, P.J., Parasitol. Today, 11 (1995) 299.

    Google Scholar 

  98. 98

    Rosenthal, P.J., Ring, C.S., Chen, X. and Cohen, F.E., J. Mol. Biol., 241 (1994) 312.

    Google Scholar 

  99. 99

    Rosenthal, P.J., Exp. Parasitol., 80 (1995) 272.

    Google Scholar 

  100. 100

    Rhoads, M.L. and Fetterer, R.H., J. Parasitol., 81 (1995) 505.

    Google Scholar 

  101. 101

    Dowd, A.J., Dalton, J.P., Loukas, A.C., Prociv, P. and Brindley, P.J., Am. J. Trop. Med. Hyg., 51 (1994) 341.

    Google Scholar 

  102. 102

    Harrop, S.A., Sawangjaroen, N., Prociv, P. and Brindley, P.J., Mol. Biochem. Parasitol., 71 (1995) 163.

    Google Scholar 

  103. 103

    Ray, C. and McKerrow, J.H., Mol. Biochem. Parasitol., 51 (1992) 239.

    Google Scholar 

  104. 104

    Larminie, C.G.C. and Johnstone, I.L., DNA Cell Biol., 15 (1996) 75.

    Google Scholar 

  105. 105

    Yamasaki, H., Kominami, E. and Aoki, T., Parasitol. Res., 78 (1992) 574.

    Google Scholar 

  106. 106

    Richer, J.K., Hunt, W.G., Sakanari, J.A. and Grieve, R.B., Exp. Parasitol., 76 (1993) 221.

    Google Scholar 

  107. 107

    Michel, A., Ghoneim, H., Resto, M., Klinkert, M.Q. and Kunz, W., Mol. Biochem. Parasitol., 73 (1995) 7.

    Google Scholar 

  108. 108

    Wasilewski, M.M., Lim, K.C., Phillips, J. and McKerrow, J.H., Mol. Biochem. Parasitol., 81 (1996) 179.

    Google Scholar 

  109. 109

    Klinkert, M.Q. and Kunz, W., Parasitol. Today, 12 (1996) 165.

    Google Scholar 

  110. 110

    Dalton, J.P. and Brindley, P.J., Parasitol. Today, 12 (1996) 165.

    Google Scholar 

  111. 111

    Wijffels, G.L., Salvatore, L., Dosen, M., Waddington, J., Wilson, L., Thompson, C., Campbell, N., Sexton, J., Wicker, J., Bowen, F., Friedel, T. and Spithill, T.W., Exp. Parasitol., 78 (1994) 132.

    Google Scholar 

  112. 112

    Newport, G.R., McKerrow, J.H., Hedstrom, R., Petit, M., McGarrigle, L., Barr, P.J. and Agabian, N., J. Biol. Chem., 263 (1988) 13179.

    Google Scholar 

  113. 113

    Talamas-Rohana, P. and Meza, I., J. Cell Biol., 106 (1988) 1787.

    Google Scholar 

  114. 114

    Vazquez, J., Franco, E., Reyes, G. and Meza, I., Cell Motil. Cytoskeleton, 32 (1995) 37.

    Google Scholar 

  115. 115

    Demeester, F., Shaw, E., Scholze, H., Stolarsky, T. and Mirelman, D., Infect. Immun., 58 (1990) 1396.

    Google Scholar 

  116. 116

    Fuller, J.D. and McDougald, L.R., J. Parasitol., 76 (1990) 464.

    Google Scholar 

  117. 117

    McKerrow, J.H., McGrath, M.E. and Engel, J.C., Parasitol. Today, 11 (1995) 279.

    Google Scholar 

  118. 118

    Cruz, A., Coburn, C.M. and Beverley, S.M., Proc. Natl. Acad. Sci. USA, 88 (1991) 7170.

    Google Scholar 

  119. 119

    Souza, A.E., Bates, P.A., Coombs, G.H. and Mottram, J.C., Mol. Biochem. Parasitol., 63 (1994) 213.

    Google Scholar 

  120. 120

    Hunter, C.A., Lockwood, B.C. and Coombs, G.H., Int. J. Parasitol., 22 (1992) 711.

    Google Scholar 

  121. 121

    Tomás, A.M. and Kelly, J.M., Mol. Biochem. Parasitol., 76 (1996) 91.

    Google Scholar 

  122. 122

    Engel, J.C. and McKerrow, J.H., Mem. Inst. Oswaldo Cruz, 90 (Suppl. I) (1995) 43.

    Google Scholar 

  123. 123

    Rosenthal, P.J., Lee, G.K. and Smith, R.E., J. Clin. Invest., 91 (1993) 1052.

    Google Scholar 

  124. 124

    Ring, C.S., Sun, E., McKerrow, J.H., Lee, G.K., Rosenthal, P.J., Kuntz, I.D. and Cohen, F.E., Proc. Natl. Acad. Sci. USA, 90 (1993) 3583.

    Google Scholar 

  125. 125

    Li, R., Kenyon, G.L., Cohen, F.E., Chen, X., Gong, B., Dominguez, J.N., Davidson, E., Kurzban, G., Miller, R.E., Nuzum, E.O., Rosenthal, P.J. and McKerrow, J.H., J. Med. Chem., 38 (1995) 5031.

    Google Scholar 

  126. 126

    Venegas, J. and Solari, A., Mol. Biochem. Parasitol., 73 (1995) 53.

    Google Scholar 

  127. 127

    Chen, M., Theander, T.G., Brogger Christensen, S., Hviid, L., Zhai, L. and Kharazmi, A., Antimicrob. Agents Chemother., 38 (1994) 1470.

    Google Scholar 

  128. 128

    Chen, M., Brogger Christensen, S., Blom, J., Lemmich, E., Nadelmann, L., Fich, K., Theander, T.G. and Kharazmi, A., Antimicrob. Agents Chemother., 37 (1993) 2550.

    Google Scholar 

  129. 129

    Zhai, L., Blom, J., Chen, M., Brogger Christensen, S. and Kharazmi, A., Antimicrob. Agents Chemother., 39 (1995) 2742.

    Google Scholar 

  130. 130

    Smith, A.M., Carmona, C., Dowd, A.J., McGonigle, S., Acosta, D. and Dalton, J.P., Parasite Immunol., 16 (1994) 325.

    Google Scholar 

  131. 131

    Urwin, P.E., Atkinson, H.J., Waller, D.A. and McPherson, M.J., Plant J., 8 (1995) 121.

    Google Scholar 

  132. 132

    Bremner, A.F., Coombs, G.H. and North, M.J., IRCS Med. Sci., 14 (1986) 555.

    Google Scholar 

  133. 133

    Yu, D., Wang, C.C. and Wang, A.L., J. Virol., 69 (1995) 2825.

    Google Scholar 

  134. 134

    Irvine, J.W., Coombs, G.H. and North, M.J., FEMS Microbiol. Lett., 96 (1992) 67.

    Google Scholar 

  135. 135

    Lustigman, S., Brotman, B., Huima, T., Prince, A.M. and McKerrow, J.H., J. Biol. Chem., 267 (1992) 17339.

    Google Scholar 

  136. 136

    Stoka, V., Nycander, M., Lenarcic, B., Labriola, C., Cazzulo, J.J., Björk, I. and Turk, V., FEBS Lett., 370 (1995) 101.

    Google Scholar 

  137. 137

    Serveau, C., Lalmanach, G., Juliano, M.A., Scharfstein, J., Juliano, L. and Gauthier, F., Biochem. J., 313 (1996) 951.

    Google Scholar 

  138. 138

    Taylor, M.A.J., Baker, K.C., Briggs, G.S., Connerton, I.F., Cummings, N.J., Pratt, K.A., Revell, D.F., Freedman, R.B. and Goodenough, P.W., Protein Eng., 8 (1995) 59.

    Google Scholar 

  139. 139

    Galvaoquintao, L., Alfieri, S.C., Ryter, A. and Rabinovitch, M., Parasitology, 101 (1990) 7.

    Google Scholar 

  140. 140

    Rabinovitch, M., Parasitol. Today, 5 (1989) 299.

    Google Scholar 

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Robertson, C.D., Coombs, G.H., North, M.J. et al. Parasite cysteine proteinases. Perspectives in Drug Discovery and Design 6, 99–118 (1996). https://doi.org/10.1007/BF02174048

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Keywords

  • Cysteine Proteinase
  • Genetic Manipulation
  • Gene Deletion
  • Future Prospect
  • Major Advance