Proteases in malaria parasites - A phylogenomic perspective

Current Genomics

Volumn 12, Issue 6, 2011, Pages 417-427

  Cai, Hong ^a   Kuang, Rui ^b   Gu, Jianying ^c   Wang, Yufeng ^a  

^a UNIVERSITY OF TEXAS AT SAN ANTONIO   (United States)

^b University of Minnesota   (United States)

^c CITY UNIVERSITY OF NEW YORK   (United States)

Author keywords

Genomics; Malaria; Phylogenomics; Plasmodium; Protease; Remote homology detection; Systems biology; Target; Vaccine

Indexed keywords

PROTEINASE; PROTEINASE INHIBITOR;

GENE TARGETING; GENETIC CONSERVATION; HUMAN; LIFE CYCLE; MALARIA; NONHUMAN; PHYLOGENOMICS; PLASMODIUM; PLASMODIUM FALCIPARUM; PROTEIN FUNCTION; PROTOZOAL GENETICS; REVIEW;

EID: 80052839347     PISSN: 13892029     EISSN: 18755488     Source Type: Journal    
DOI: 10.2174/138920211797248565     Document Type: Review

References (113)

1. Dvorin, J. D.; Martyn, D. C.; Patel, S. D.; Grimley, J. S.; Collins, C. R.; Hopp, C. S.; Bright, A. T.; Westenberger, S.; Winzeler, E.; Blackman, M. J.; Baker, D. A.; Wandless, T. J.; Duraisingh, M. T. A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes. Science, 2010, 328(5980), 910-912.
2. Ecker, A.; Lakshmanan, V.; Sinnis, P.; Coppens, I.; Fidock, D. A. Evidence That Mutant PfCRT Facilitates the Transmission to Mosquitoes of Chloroquine-Treated Plasmodium Gametocytes. J. Infect. Dis., 2011, 203(2), 228-236.
3. Jana, S.; Paliwal, J. Novel molecular targets for antimalarial chemotherapy. Int. J. Antimicrob. Agents, 2007, 30(1), 4-10.
4. Joet, T.; Eckstein-Ludwig, U.; Morin, C.; Krishna, S. Validation of the hexose transporter of Plasmodium falciparum as a novel drug target. Proc. Natl. Acad. Sci. USA, 2003, 100(13), 7476-7479.
5. Johnson, D. J.; Fidock, D. A.; Mungthin, M.; Lakshmanan, V.; Sidhu, A. B.; Bray, P. G.; Ward, S. A. Evidence for a central role for PfCRT in conferring Plasmodium falciparum resistance to diverse antimalarial agents. Mol. Cell, 2004, 15(6), 867-877.
6. Kirk, K.; Howitt, S. M.; Broer, S.; Saliba, K. J.; Downie, M. J. Purine uptake in Plasmodium: transport versus metabolism. Trends Parasitol, 2009, 25(6), 246-249.
7. Patel, A. P.; Staines, H. M.; Krishna, S. New antimalarial targets: the example of glucose transport. Travel Med. Infect. Dis., 2008, 6(1-2), 58-66.
8. Rangarajan, R.; Bei, A.; Henry, N.; Madamet, M.; Parzy, D.; Nivez, M. P.; Doerig, C.; Sultan, A. Pbcrk-1, the Plasmodium berghei orthologue of P. falciparum cdc-2 related kinase-1 (Pfcrk-1), is essential for completion of the intraerythrocytic asexual cycle. Exp. Parasitol., 2006, 112(3), 202-207.
9. Dorin, D.; Semblat, J. P.; Poullet, P.; Alano, P.; Goldring, J. P.; Whittle, C.; Patterson, S.; Chakrabarti, D.; Doerig, C. PfPK7, an atypical MEK-related protein kinase, reflects the absence of classical three-component MAPK pathways in the human malaria parasite Plasmodium falciparum. Mol. Microbiol., 2005, 55(1), 184-196.
10. Merckx, A.; Le Roch, K.; Nivez, M. P.; Dorin, D.; Alano, P.; Gutierrez, G. J.; Nebreda, A. R.; Goldring, D.; Whittle, C.; Patterson, S.; Chakrabarti, D.; Doerig, C. Identification and initial characterization of three novel cyclin-related proteins of the human malaria parasite Plasmodium falciparum. J. Biol. Chem., 2003, 278(41), 39839-39850.
11. Morgan, D. O. Cyclin-dependent kinases: engines, clocks, and microprocessors. Annu. Rev. Cell Dev. Biol., 1997, 13, 261-291.
12. Grant, K. M. Targeting the cell cycle in the pursuit of novel chemotherapies against parasitic protozoa. Curr. Pharm. Des., 2008, 14(9), 917-924.
13. Koyama, F. C.; Chakrabarti, D.; Garcia, C. R. Molecular machinery of signal transduction and cell cycle regulation in Plasmodium. Mol. Biochem. Parasitol., 2009, 165(1), 1-7.
14. Kozlov, S.; Waters, N. C.; Chavchich, M. Leveraging cell cycle analysis in anticancer drug discovery to identify novel plasmodial drug targets. Infect. Disord. Drug Targets, 2010, 10(3), 165-190.
15. Holland, Z.; Prudent, R.; Reiser, J. B.; Cochet, C.; Doerig, C. Functional analysis of protein kinase CK2 of the human malaria parasite Plasmodium falciparum. Eukaryot. Cell, 2009, 8(3), 388-397.
16. Merckx, A.; Echalier, A.; Langford, K.; Sicard, A.; Langsley, G.; Joore, J.; Doerig, C.; Noble, M.; Endicott, J. Structures of P. falciparum protein kinase 7 identify an activation motif and leads for inhibitor design. Structure, 2008, 16(2), 228-238.
17. Waters, N. C.; Geyer, J. A. Cyclin-dependent protein kinases as therapeutic drug targets for antimalarial drug development. Expert. Opin. Ther. Targets, 2003, 7(1), 7-17.
18. Keenan, S. M.; Geyer, J. A.; Welsh, W. J.; Prigge, S. T.; Waters, N. C. Rational inhibitor design and iterative screening in the identification of selective plasmodial cyclin dependent kinase inhibitors. Comb. Chem. High Throughput Screen., 2005, 8(1), 27-38.
19. Jomaa, H.; Wiesner, J.; Sanderbrand, S.; Altincicek, B.; Weidemeyer, C.; Hintz, M.; Turbachova, I.; Eberl, M.; Zeidler, J.; Lichtenthaler, H. K.; Soldati, D.; Beck, E. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science, 1999, 285(5433), 1573-1576.
20. Wiesner, J.; Jomaa, H. Isoprenoid biosynthesis of the apicoplast as drug target. Curr. Drug Targets, 2007, 8(1), 3-13.
21. Dahl, E. L.; Rosenthal, P. J. Apicoplast translation, transcription and genome replication: targets for antimalarial antibiotics. Trends Parasitol., 2008, 24(6), 279-284.
22. Coombs, G. H.; Goldberg, D. E.; Klemba, M.; Berry, C.; Kay, J.; Mottram, J. C. Aspartic proteases of Plasmodium falciparum and other parasitic protozoa as drug targets. Trends Parasitol., 2001, 17(11), 532-537.
23. Goldberg, D. E. Hemoglobin degradation. Curr. Top. Microbiol. Immunol., 2005, 295, 275-291.
24. Rosenthal, P. J. Hydrolysis of erythrocyte proteins by proteases of malaria parasites. Curr. Opin. Hematol., 2002, 9(2), 140-145.
25. Rosenthal, P. J. Cysteine proteases of malaria parasites. Int. J. Parasitol., 2004, 34(13/14), 1489-1499.
26. Eggleson, K. K.; Duffin, K. L.; Goldberg, D. E. Identification and characterization of falcilysin, a metallopeptidase involved in hemoglobin catabolism within the malaria parasite Plasmodium falciparum. J. Biol. Chem., 1999, 274(45), 32411-32417.
27. Murata, C. E.; Goldberg, D. E. Plasmodium falciparum falcilysin: a metalloprotease with dual specificity. J. Biol. Chem., 2003, 278(39), 38022-38028.
28. Murata, C. E.; Goldberg, D. E. Plasmodium falciparum falcilysin: an unprocessed food vacuole enzyme. Mol. Biochem. Parasitol., 2003, 129(1), 123-126.
29. Blackman, M. J. Proteases involved in erythrocyte invasion by the malaria parasite: function and potential as chemotherapeutic targets. Curr. Drug Targets, 2000, 1(1), 59-83.
30. Blackman, M. J. Malarial proteases and host cell egress: an 'emerging' cascade. Cell Microbiol., 2008, 10(10), 1925-1934.
31. Blackman, M. J.; Fujioka, H.; Stafford, W. H.; Sajid, M.; Clough, B.; Fleck, S. L.; Aikawa, M.; Grainger, M.; Hackett, F. A subtilisin-like protein in secretory organelles of Plasmodium falciparum merozoites. J. Biol. Chem., 1998, 273(36), 23398-23409.
32. Withers-Martinez, C.; Jean, L.; Blackman, M. J. Subtilisin-like proteases of the malaria parasite. Mol. Microbiol., 2004, 53(1), 55-63.
33. Baker, R. P.; Wijetilaka, R.; Urban, S. Two Plasmodium rhomboid proteases preferentially cleave different adhesins implicated in all invasive stages of malaria. PLoS Pathog, 2006, 2(10), e113.
34. Le Chat, L.; Sinden, R. E.; Dessens, J. T. The role of metacaspase 1 in Plasmodium berghei development and apoptosis. Mol. Biochem. Parasitol., 2007, 153(1), 41-47.
35. O'Donnell, R. A.; Hackett, F.; Howell, S. A.; Treeck, M.; Struck, N.; Krnajski, Z.; Withers-Martinez, C.; Gilberger, T. W.; Blackman, M. J. Intramembrane proteolysis mediates shedding of a key adhesin during erythrocyte invasion by the malaria parasite. J. Cell Biol., 2006, 174(7), 1023-1033.
36. Dunn, B.; Marzahn, M.; Liu, P.; Gutierrez-de-Teran, H.; Robbins, A.; McKenna, R. Plasmepsin 9 as a New Target for Antimalarial Drug Discovery. Biopolymers, 2009, 92(4), 347-347.
37. Liu, P.; Marzahn, M. R.; Robbins, A. H.; Gutierrez-de-Teran, H.; Rodriguez, D.; McClung, S. H.; Stevens, S. M.; Yowell, C. A.; Dame, J. B.; McKenna, R.; Dunn, B. M. Recombinant Plasmepsin 1 from the Human Malaria Parasite Plasmodium falciparum: Enzymatic Characterization, Active Site Inhibitor Design, and Structural Analysis. Biochemistry, 2009, 48(19), 4086-4099.
38. Shah, F.; Mukherjee, P.; Gut, J.; Legac, J.; Rosenthal, P. J.; Tekwani, B. L.; Avery, M. A. Identification of Novel Malarial Cysteine Protease Inhibitors Using Structure-Based Virtual Screening of a Focused Cysteine Protease Inhibitor Library. J. Chem. Inf. Model., 2011, 51(4), 852-864.
39. Carroll, C. D.; Patel, H.; Johnson, T. O.; Guo, T.; Orlowski, M.; He, Z. M.; Cavallaro, C. L.; Guo, J.; Oksman, A.; Gluzman, I. Y.; Connelly, J.; Chelsky, D.; Goldberg, D. E.; Dolle, R. E. Identification of potent inhibitors of Plasmodium falciparum plasmepsin II from an encoded statine combinatorial library. Bioorg. Med. Chem. Lett., 1998, 8(17), 2315-2320.
40. Haque, T. S.; Skillman, A. G.; Lee, C. E.; Habashita, H.; Gluzman, I. Y.; Ewing, T. J.; Goldberg, D. E.; Kuntz, I. D.; Ellman, J. A. Potent, low-molecular-weight non-peptide inhibitors of malarial aspartyl protease plasmepsin II. J. Med. Chem., 1999, 42(8), 1428-1440.
41. Kasam, V.; Zimmermann, M.; Maass, A.; Schwichtenberg, H.; Wolf, A.; Jacq, N.; Breton, V.; Hofmann-Apitius, M. Design of new plasmepsin inhibitors: a virtual high throughput screening approach on the EGEE grid. J. Chem. Inf. Model., 2007, 47(5), 1818-1828.
42. Li, R.; Chen, X.; Gong, B.; Selzer, P. M.; Li, Z.; Davidson, E.; Kurzban, G.; Miller, R. E.; Nuzum, E. O.; McKerrow, J. H.; Fletterick, R. J.; Gillmor, S. A.; Craik, C. S.; Kuntz, I. D.; Cohen, F. E.; Kenyon, G. L. Structure-based design of parasitic protease inhibitors. Bioorg. Med. Chem., 1996, 4(9), 1421-1427.
43. Pandey, K. C.; Barkan, D. T.; Sali, A.; Rosenthal, P. J. Regulatory Elements within the Prodomain of Falcipain-2, a Cysteine Protease of the Malaria Parasite Plasmodium falciparum. Plos One, 2009, 4(5), e5694.
44. Scheidt, K. A.; Roush, W. R.; McKerrow, J. H.; Selzer, P. M.; Hansell, E.; Rosenthal, P. J. Structure-based design, synthesis and evaluation of conformationally constrained cysteine protease inhibitors. Bioorg. Med. Chem., 1998, 6(12), 2477-2494.
45. Eisen, J. A. Phylogenomics: improving functional predictions for uncharacterized genes by evolutionary analysis. Genome Res., 1998, 8(3), 163-167.
46. Eisen, J. A.; Fraser, C. M. Phylogenomics: intersection of evolution and genomics. Science, 2003, 300(5626), 1706-1707.
47. Kuang, R.; Gu, J.; Cai, H.; Wang, Y. Improved prediction of malaria degradomes by supervised learning with SVM and profile kernel. Genetica, 2009, 136(1), 189-209.
48. Gardner, M. J.; Hall, N.; Fung, E.; White, O.; Berriman, M.; Hyman, R. W.; Carlton, J. M.; Pain, A.; Nelson, K. E.; Bowman, S.; Paulsen, I. T.; James, K.; Eisen, J. A.; Rutherford, K.; Salzberg, S. L.; Craig, A.; Kyes, S.; Chan, M. S.; Nene, V.; Shallom, S. J.; Suh, B.; Peterson, J.; Angiuoli, S.; Pertea, M.; Allen, J.; Selengut, J.; Haft, D.; Mather, M. W.; Vaidya, A. B.; Martin, D. M. A.; Fairlamb, A. H.; Fraunholz, M. J.; Roos, D. S.; Ralph, S. A.; McFadden, G. I.; Cummings, L. M.; Subramanian, G. M.; Mungall, C.; Venter, J. C.; Carucci, D. J.; Hoffman, S. L.; Newbold, C.; Davis, R. W.; Fraser, C. M.; Barrell, B. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature, 2002, 419(6906), 498-511.
49. Altschul, S. F.; Madden, T. L.; Schaffer, A. A.; Zhang, J.; Zhang, Z.; Miller, W.; Lipman, D. J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res., 1997, 25(17), 3389-3402.
50. Karplus, K.; Barrett, C.; Hughey, R. Hidden Markov models for detecting remote protein homologies. Bioinformatics, 1998, 14(10), 846-856.
51. Sadreyev, R.; Grishin, N. COMPASS: a tool for comparison of multiple protein alignments with assessment of statistical significance. J. Mol. Biol., 2003, 326(1), 317-336.
52. Soding, J. Protein homology detection by HMM-HMM comparison. Bioinformatics, 2005, 21(7), 951-960.
53. Chubb, D.; Jefferys, B. R.; Sternberg, M. J.; Kelley, L. A. Sequencing delivers diminishing returns for homology detection: implications for mapping the protein universe. Bioinformatics, 2010, 26(21), 2664-2671.
54. Qi, Y.; Sadreyev, R. I.; Wang, Y.; Kim, B. H.; Grishin, N. V. A comprehensive system for evaluation of remote sequence similarity detection. BMC Bioinformatics, 2007, 8, 314.
55. Reid, A. J.; Yeats, C.; Orengo, C. A. Methods of remote homology detection can be combined to increase coverage by 10% in the midnight zone. Bioinformatics, 2007, 23(18), 2353-2360.
56. Wu, Y. M.; Wang, X. Y.; Liu, X.; Wang, Y. F. Data-mining approaches reveal hidden families of proteases in the genome of malaria parasite. Genome Res., 2003, 13(4), 601-616.
57. Wang, Y.; Wu, Y. Computer assisted searches for drug targets with emphasis on malarial proteases and their inhibitors. Curr. Drug Targets Infect. Disord., 2004, 4(1), 25-40.
58. Carlton, J. M.; Adams, J. H.; Silva, J. C.; Bidwell, S. L.; Lorenzi, H.; Caler, E.; Crabtree, J.; Angiuoli, S. V.; Merino, E. F.; Amedeo, P.; Cheng, Q.; Coulson, R. M.; Crabb, B. S.; Del Portillo, H. A.; Essien, K.; Feldblyum, T. V.; Fernandez-Becerra, C.; Gilson, P. R.; Gueye, A. H.; Guo, X.; Kang'a, S.; Kooij, T. W.; Korsinczky, M.; Meyer, E. V.; Nene, V.; Paulsen, I.; White, O.; Ralph, S. A.; Ren, Q.; Sargeant, T. J.; Salzberg, S. L.; Stoeckert, C. J.; Sullivan, S. A.; Yamamoto, M. M.; Hoffman, S. L.; Wortman, J. R.; Gardner, M. J.; Galinski, M. R.; Barnwell, J. W.; Fraser-Liggett, C. M. Comparative genomics of the neglected human malaria parasite Plasmodium vivax. Nature, 2008, 455(7214), 757-763.
59. Carlton, J.; Silva, J.; Hall, N. The genome of model malaria parasites, and comparative genomics. Curr. Issues Mol. Biol., 2005, 7(1), 23-37.
60. Carlton, J. M.; Angiuoli, S. V.; Suh, B. B.; Kooij, T. W.; Pertea, M.; Silva, J. C.; Ermolaeva, M. D.; Allen, J. E.; Selengut, J. D.; Koo, H. L.; Peterson, J. D.; Pop, M.; Kosack, D. S.; Shumway, M. F.; Bidwell, S. L.; Shallom, S. J.; van Aken, S. E.; Riedmuller, S. B.; Feldblyum, T. V.; Cho, J. K.; Quackenbush, J.; Sedegah, M.; Shoaibi, A.; Cummings, L. M.; Florens, L.; Yates, J. R.; Raine, J. D.; Sinden, R. E.; Harris, M. A.; Cunningham, D. A.; Preiser, P. R.; Bergman, L. W.; Vaidya, A. B.; Van Lin, L. H.; Janse, C. J.; Waters, A. P.; Smith, H. O.; White, O. R.; Salzberg, S. L.; Venter, J. C.; Fraser, C. M.; Hoffman, S. L.; Gardner, M. J.; Carucci, D. J. Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii. Nature, 2002, 419(6906), 512-519.
61. Iyer, L. M.; Koonin, E. V.; Aravind, L. Novel predicted peptidases with a potential role in the ubiquitin signaling pathway. Cell Cycle, 2004, 3(11), 1440-1450.
62. Rawlings, N. D. A large and accurate collection of peptidase cleavages in the MEROPS database. Database (Oxford), 2009, 2009, bap015.
63. Boddey, J. A.; Hodder, A. N.; Gunther, S.; Gilson, P. R.; Patsiouras, H.; Kapp, E. A.; Pearce, J. A.; de Koning-Ward, T. F.; Simpson, R. J.; Crabb, B. S.; Cowman, A. F. An aspartyl protease directs malaria effector proteins to the host cell. Nature, 2010, 463(7281), 627-31.
64. McGowan, S.; Oellig, C. A.; Birru, W. A.; Caradoc-Davies, T. T.; Stack, C. M.; Lowther, J.; Skinner-Adams, T.; Mucha, A.; Kafarski, P.; Grembecka, J.; Trenholme, K. R.; Buckle, A. M.; Gardiner, D. L.; Dalton, J. P.; Whisstock, J. C. Structure of the Plasmodium falciparum M17 aminopeptidase and significance for the design of drugs targeting the neutral exopeptidases. Proc. Natl. Acad. Sci.USA, 2010, 107(6), 2449-2454.
65. Moon, S. U.; Kang, J. M.; Kim, T. S.; Kong, Y.; Sohn, W. M.; Na, B. K. Plasmodium vivax: collaborative roles for plasmepsin 4 and vivapains in hemoglobin hydrolysis. Exp. Parasitol., 2011, 128(2), 127-132.
66. Silmon de Monerri, N. C.; Flynn, H. R.; Campos, M. G.; Hackett, F.; Koussis, K.; Withers-Martinez, C.; Skehel, J. M.; Blackman, M. J. Global identification of multiple substrates for Plasmodium falciparum SUB1, an essential malarial processing protease. Infect. Immun., 2011, 79(3), 1086-1097.
67. Skinner-Adams, T. S.; Stack, C. M.; Trenholme, K. R.; Brown, C. L.; Grembecka, J.; Lowther, J.; Mucha, A.; Drag, M.; Kafarski, P.; McGowan, S.; Whisstock, J. C.; Gardiner, D. L.; Dalton, J. P. Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials. Trends Biochem. Sci., 2010, 35(1), 53-61.
68. Sologub, L.; Kuehn, A.; Kern, S.; Przyborski, J.; Schillig, R.; Pradel, G. Malaria proteases mediate inside-out egress of gametocytes from red blood cells following parasite transmission to the mosquito. Cell Microbiol., 2011, 13(6), 897-912.
69. Wang, F.; Krai, P.; Deu, E.; Bibb, B.; Lauritzen, C.; Pedersen, J.; Bogyo, M.; Klemba, M. Biochemical characterization of Plasmodium falciparum dipeptidyl aminopeptidase 1. Mol. Biochem. Parasitol., 2011, 175(1), 10-20.
70. Brown, D.; Sjolander, K. Functional classification using phylogenomic inference. PLoS Comput. Biol., 2006, 2(6), e77.
71. Sjolander, K. Phylogenomic inference of protein molecular function: advances and challenges. Bioinformatics, 2004, 20(2), 170-179.
72. Brown, J. R.; Auger, K. R. Phylogenomics of phosphoinositide lipid kinases: perspectives on the evolution of second messenger signaling and drug discovery. BMC Evol. Biol., 2011, 11, 4.
73. Gillespie, J. J.; Brayton, K. A.; Williams, K. P.; Diaz, M. A.; Brown, W. C.; Azad, A. F.; Sobral, B. W. Phylogenomics reveals a diverse Rickettsiales type IV secretion system. Infect. Immun., 2010, 78(5), 1809-1823.
74. Jung, K. H.; Cao, P.; Seo, Y. S.; Dardick, C.; Ronald, P. C. The Rice Kinase Phylogenomics Database: a guide for systematic analysis of the rice kinase super-family. Trends Plant Sci., 2010, 15(11), 595-599.
75. Hu, G.; Leger, R. J. A phylogenomic approach to reconstructing the diversification of serine proteases in fungi. J. Evol. Biol., 2004, 17(6), 1204-1214.
76. Kordis, D.; Turk, V. Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes. BMC Evol. Biol., 2009, 9, 266.
77. Wang, Y. F.; Gu, X. Functional divergence in the caspase gene family and altered functional constraints: Statistical analysis and prediction. Genetics, 2001, 158(3), 1311-1320.
78. Russo, I.; Oksman, A.; Vaupel, B.; Goldberg, D. E. A calpain unique to alveolates is essential in Plasmodium falciparum and its knockdown reveals an involvement in pre-S-phase development. Proc. Natl. Acad. Sci. USA, 2009, 106(5), 1554-1559.
79. Wu, Y.; Wang, X.; Liu, X.; Wang, Y. Data-mining approaches reveal hidden families of proteases in the genome of malaria parasite. Genome Res., 2003, 13(4), 601-616.
80. Meslin, B.; Barnadas, C.; Boni, V.; Latour, C.; De Monbrison, F.; Kaiser, K.; Picot, S. Features of apoptosis in Plasmodium falciparum erythrocytic stage through a putative role of PfMCA1 metacaspase-like protein. J. Infect. Dis., 2007, 195(12), 1852-1859.
81. Meslin, B.; Zalila, H.; Fasel, N.; Picot, S.; Bienvenu, A. L. Are protozoan metacaspases potential parasite killers? Parasit. Vectors, 2011, 4(1), 26.
82. von Mering, C.; Jensen, L. J.; Snel, B.; Hooper, S. D.; Krupp, M.; Foglierini, M.; Jouffre, N.; Huynen, M. A.; Bork, P. STRING: known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Res., 2005, 33 (Database issue), D433-7.
83. LaCount, D. J.; Vignali, M.; Chettier, R.; Phansalkar, A.; Bell, R.; Hesselberth, J. R.; Schoenfeld, L. W.; Ota, I.; Sahasrabudhe, S.; Kurschner, C.; Fields, S.; Hughes, R. E. A protein interaction network of the malaria parasite Plasmodium falciparum. Nature, 2005, 438(7064), 103-107.
84. Szklarczyk, D.; Franceschini, A.; Kuhn, M.; Simonovic, M.; Roth, A.; Minguez, P.; Doerks, T.; Stark, M.; Muller, J.; Bork, P.; Jensen, L. J.; von Mering, C. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res., 2010, 39 (Database issue), D561-8.
85. Elmendorf, H. G.; Haldar, K. Identification and localization of ERD2 in the malaria parasite Plasmodium falciparum: separation from sites of sphingomyelin synthesis and implications for organization of the Golgi. EMBO J., 1993, 12(12), 4763-4773.
86. Couffin, S.; Hernandez-Rivas, R.; Blisnick, T.; Mattei, D. Characterisation of Pf Sec61, a Plasmodium falciparum homologue of a component of the translocation machinery at the endoplasmic reticulum membrane of eukaryotic cells. Mol. Biochem. Parasitol., 1998, 92(1), 89-98.
87. Li, X.; Chen, H.; Bahamontes-Rosa, N.; Kun, J. F.; Traore, B.; Crompton, P. D.; Chishti, A. H. Plasmodium falciparum signal peptide peptidase is a promising drug target against blood stage malaria. Biochem. Biophys. Res. Commun., 2009, 380(3), 454-459.
88. Li, X.; Chen, H.; Oh, S. S.; Chishti, A. H. A Presenilin-like protease associated with Plasmodium falciparum micronemes is involved in erythrocyte invasion. Mol. Biochem. Parasitol., 2008, 158(1), 22-31.
89. Jean, L.; Long, M.; Young, J.; Pery, P.; Tomley, F. Aspartyl proteinase genes from apicomplexan parasites: evidence for evolution of the gene structure. Trends Parasitol., 2001, 17(10), 491-498.
90. Banerjee, R.; Liu, J.; Beatty, W.; Pelosof, L.; Klemba, M.; Goldberg, D. E. Four plasmepsins are active in the Plasmodium falciparum food vacuole, including a protease with an active-site histidine. Proc. Natl. Acad. Sci.USA, 2002, 99(2), 990-995.
91. Skinner-Adams, T. S.; Stack, C. M.; Trenholme, K. R.; Brown, C. L.; Grembecka, J.; Lowther, J.; Mucha, A.; Drag, M.; Kafarski, P.; McGowan, S.; Whisstock, J. C.; Gardiner, D. L.; Dalton, J. P. Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials. Trends Biochem. Sci., 2010, 35(1), 53-61.
92. McGowan, S.; Oellig, C. A.; Birru, W. A.; Caradoc-Davies, T. T.; Stack, C. M.; Lowther, J.; Skinner-Adams, T.; Mucha, A.; Kafarski, P.; Grembecka, J.; Trenholme, K. R.; Buckle, A. M.; Gardiner, D. L.; Dalton, J. P.; Whisstock, J. C. Structure of the Plasmodium falciparum M17 aminopeptidase and significance for the design of drugs targeting the neutral exopeptidases. Proc. Natl. Acad. Sci. USA, 2010, 107(6), 2449-2454.
93. Harris, P. K.; Yeoh, S.; Dluzewski, A. R.; O'Donnell, R. A.; Withers-Martinez, C.; Hackett, F.; Bannister, L. H.; Mitchell, G. H.; Blackman, M. J. Molecular identification of a malaria merozoite surface sheddase. Plos Pathogens, 2005, 1(3), 241-251.
94. Jean, L.; Hackett, F.; Martin, S. R.; Blackman, M. J. Functional characterization of the propeptide of Plasmodium falciparum subtilisin-like protease-1. J. Biol. Chem., 2003, 278(31), 28572-28579.
95. Jean, L.; Withers-Martinez, C.; Hackett, F.; Blackman, M. J. Unique insertions within Plasmodium falciparum subtilisin-like protease-1 are crucial for enzyme maturation and activity. Mol. Biochem. Parasitol., 2005, 144(2), 187-197.
96. Shenai, B. R.; Sijwali, P. S.; Singh, A.; Rosenthal, P. J. Characterization of native and recombinant falcipain-2, a principal trophozoite cysteine protease and essential hemoglobinase of Plasmodium falciparum. J. Biol. Chem., 2000, 275(37), 29000-29010.
97. Sijwali, P. S.; Rosenthal, P. J. Gene disruption confirms a critical role for the cysteine protease falcipain-2 in hemoglobin hydrolysis by Plasmodium falciparum. Proc. Natl. Acad. Sci. USA, 2004, 101(13), 4384-4389.
98. Sijwali, P. S.; Koo, J.; Singh, N.; Rosenthal, P. J. Gene disruptions demonstrate independent roles for the four falcipain cysteine proteases of Plasmodium falciparum. Mol. Biochem. Parasitol., 2006, 150(1), 96-106.
99. Brossier, F.; Jewett, T. J.; Sibley, L. D.; Urban, S. A spatially localized rhomboid protease cleaves cell surface adhesins essential for invasion by Toxoplasma. Proc. Natl. Acad. Sci. USA, 2005, 102(11), 4146-4151.
100. Dowse, T. J.; Pascall, J. C.; Brown, K. D.; Soldati, D. Apicomplexan rhomboids have a potential role in microneme protein cleavage during host cell invasion. Int. J. Parasitol., 2005, 35(7), 747-756.
101. Srinivasan, P.; Coppens, I.; Jacobs-Lorena, M. Distinct roles of Plasmodium rhomboid 1 in parasite development and malaria pathogenesis. PLoS Pathog, 2009, 5(1), e1000262.
102. Dowse, T. J.; Soldati, D. Rhomboid-like proteins in Apicomplexa: phylogeny and nomenclature. Trends Parasitol., 2005, 21(6), 254-258.
103. Ralph, S. A.; Foth, B. J.; Hall, N.; McFadden, G. I. Evolutionary pressures on apicoplast transit peptides. Mol. Biol. Evol., 2004, 21(12), 2183-2194.
104. Ralph, S. A.; van Dooren, G. G.; Waller, R. F.; Crawford, M. J.; Fraunholz, M. J.; Foth, B. J.; Tonkin, C. J.; Roos, D. S.; McFadden, G. I. Tropical infectious diseases: metabolic maps and functions of the Plasmodium falciparum apicoplast. Nat. Rev. Microbiol., 2004, 2(3), 203-216.
105. Zuegge, J.; Ralph, S.; Schmuker, M.; McFadden, G. I.; Schneider, G. Deciphering apicoplast targeting signals--feature extraction from nuclear-encoded precursors of Plasmodium falciparum apicoplast proteins. Gene, 2001, 280(1/2), 19-26.
106. Foth, B. J.; Ralph, S. A.; Tonkin, C. J.; Struck, N. S.; Fraunholz, M.; Roos, D. S.; Cowman, A. F.; McFadden, G. I. Dissecting apicoplast targeting in the malaria parasite Plasmodium falciparum. Science, 2003, 299(5607), 705-708.
107. Nielsen, H.; Engelbrecht, J.; Brunak, S.; von Heijne, G. Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Eng., 1997, 10(1), 1-6.
108. El Bakkouri, M.; Pow, A.; Mulichak, A.; Cheung, K. L.; Artz, J. D.; Amani, M.; Fell, S.; de Koning-Ward, T. F.; Goodman, C. D.; McFadden, G. I.; Ortega, J.; Hui, R.; Houry, W. A. The Clp chaperones and proteases of the human malaria parasite Plasmodium falciparum. J. Mol. Biol., 2010, 404(3), 456-477.
109. Rathore, S.; Sinha, D.; Asad, M.; Bottcher, T.; Afrin, F.; Chauhan, V. S.; Gupta, D.; Sieber, S. A.; Mohmmed, A. A cyanobacterial serine protease of Plasmodium falciparum is targeted to the apicoplast and plays an important role in its growth and development. Mol. Microbiol., 2010, 77(4), 873-890.
110. Bottcher, T.; Sieber, S. A. Beta-lactones as specific inhibitors of ClpP attenuate the production of extracellular virulence factors of Staphylococcus aureus. J. Am. Chem. Soc., 2008, 130(44), 14400-14401.
111. Saitou, N.; Nei, M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol., 1987, 4(4), 406-425.
112. Tamura, K.; Peterson, D.; Peterson, N.; Stecher, G.; Nei, M.; Kumar, S. MEGA5: Molecular Evolutionary Genetics Analysis using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods. Mol. Biol. Evol., 2011.
113. Smoot, M. E.; Ono, K.; Ruscheinski, J.; Wang, P. L.; Ideker, T. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics, 2010, 27(3), 431-432.