Malaria and Antimalarials - A Focused View

Antiparasitic and Antibacterial Drug Discovery: From Molecular Targets to Drug Candidates

Volumn , Issue , 2009, Pages 277-298

  Seeber, Frank ^a  

^a HUMBOLDT UNIVERSITY   (Germany)

Author keywords

Apicoplast; Chemotherapeutics; Fatty acid biosynthesis; Ferredoxin; Isoprenoids; Malaria; Plasmodium falciparum; Toxoplasma gondii

Indexed keywords

EID: 77957918295     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9783527626816.ch15     Document Type: Chapter

References (113)

1. Russell, P.F. (1955) Man's Mastery of Malaria, Oxford Univ. Press, London.
2. World Health Organization (2005) World malaria report 2005, Roll Back Malaria, World Health Organization UNICEF, Geneva.
3. Butcher, G.A. (2005) T-cell depletion and immunity to malaria in HIV-infections. Parasitology, 130, 141-150.
4. Catteruccia, F. (2007) Malaria vector control in the third millennium: progress and perspectives of molecular approaches. Pest Management Science, 63, 634-640.
5. World Health Organization (2006) Resistance to antimalarials (Annex 6), Guidelines for the Treatment of Malaria, WHO, Geneva, pp. 155-184.
6. Talisuna, A.O., Bloland, P. and D'Alessandro, U. (2004) History, dynamics, and public health importance of malaria parasite resistance. Clinical Microbiology Reviews, 17, 235-254.
7. Frearson, J.A., Wyatt, P.G., Gilbert, I.H. and Fairlamb, A.H. (2007) Target assessment for antiparasitic drug discovery. Trends in Parasitology, 23, 589-595.
8. Ashburner, M. (2003) A hat trick-Plasmodium, Anopheles and Homo. Genome Biology, 4, 103.
9. Hoffman, S.L., Subramanian, G.M., Collins, F.H. and Venter, J.C. (2002) Plasmodium, human and Anopheles genomics and malaria. Nature, 415, 702-709.
10. Cooper, R.A. and Carucci, D.J. (2004) Proteomic approaches to studying drug targets and resistance in Plasmodium. Current Drug Targets-Infectious Disorders, 4, 41-51.
11. Greenwood, B.M., Bojang, K., Whitty, C.J. and Targett, G.A. (2005) Malaria. Lancet, 365, 1487-1498.
12. Schlitzer, M. (2007) Malaria chemotherapeutics part I: History of antimalarial drug development, currently used therapeutics, and drugs in clinical development. ChemMedChem, 2, 944-986.
13. Schlitzer, M. (2008) Antimalarial drugs-what is in use and what is in the pipeline. Archiv der Pharmazie (Weinheim), 341, 149-163.
14. Wiesner, J., Ortmann, R., Jomaa, H. and Schlitzer, M. (2003) New antimalarial drugs. Angewandte Chemie (International Edition in English), 42, 5274-5293.
15. Winstanley, P. and Ward, S. (2006) Malaria chemotherapy. Advances in Parasitology, 61, 47-76.
16. Gardner, M.J., Hall, N., Fung, E., White, O., Berriman, M., Hyman, R.W., Carlton, J.M. et al. (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature, 419, 498-511.
17. Keller, T.H., Pichota, A. and Yin, Z. (2006) A practical view of "druggability". Current Opinion in Chemical Biology, 10, 357-361.
18. Hyde, J.E. (2007) Targeting purine and pyrimidine metabolism in human apicomplexan parasites. Current Drug Targets, 8, 31-47.
19. Kirk, K. and Saliba, K.J. (2007) Targeting nutrient uptake mechanisms in Plasmodium. Current DrugTargets, 8, 75-88.
20. Mather, M.W., Henry, K.W. and Vaidya, A.B. (2007) Mitochondrial drug targets in apicomplexan parasites. Current Drug Targets, 8, 49-60.
21. Morgan, R.E., Evans, K.M., Patterson, S., Catti, F., Ward, G.E. and Westwood, N.J. (2007) Targeting invasion and egress: from tools to drugs? Current Drug Targets, 8, 61-74.
22. Linares, G.E. and Rodriguez, J.B. (2007) Current status and progresses made in malaria chemotherapy. Current Medicinal Chemistry, 14, 289-314.
23. Sahu, N.K., Sahu, S. and Kohli, D.V. (2008) Novel molecular targets for antimalarial drug development. Chemical Biology and Drug Design, 71, 287-297.
24. Müller, I.B., Das Gupta, R., Luersen, K., Wrenger, C. and Walter, R.D. (2008) Assessing the polyamine metabolism of Plasmodium falciparum as chemotherapeutic target. Molecular and Biochemical Parasitology, 160, 1-7.
25. Wilson, R.J., Williamson, D.H. and Preiser, P. (1994) Malaria and other Apicomplexans: the "plant" connection. Infectious Agents and Disease, 3, 29-37.
26. Kohler, S., Delwiche, C.F., Denny, P.W., Tilney, L.G., Webster, P., Wilson, R.J., Palmer, J.D. et al. (1997) Aplastid of probable green algal origin in Apicomp-lexan parasites. Science, 275, 1485-1489.
27. McFadden, G.I., Reith, M.E., Munholland, J. and Lang-Unnasch, N. (1996) Plastid in human parasites. Nature, 381, 482.
28. Wilson, R.J. (2005) Parasite plastids: approaching the endgame. Biological Reviews of the Cambridge Philosophical Society, 80, 129-153.
29. Waller, R.F. and McFadden, G.I. (2005) The apicoplast: a review of the derived plastid of apicomplexan parasites. Current Issues in Molecular Biology, 7, 57-79.
30. Wiesner, J. and Seeber, F. (2005) The plastid-derived organelle of protozoan human parasites as a target of established and emerging drugs. Expert Opinion on Therapeutic Targets, 9, 23-44.
31. Dahl, E.L. and Rosenthal, P.J. (2008) Apicoplast translation, transcription and genome replication: targets for antimalarial antibiotics. Trends in Parasitology, 24, 279-284.
32. Tonkin, C.J., Kalanon, M. and McFadden, G.I. (2008) Protein targeting to the malaria parasite plastid. Traffic (Copenhagen, Denmark), 9, 166-175.
33. Ralph, S.A., Van Dooren, G.G., Waller, R.F., Crawford, M.J., Fraunholz, M.J., Foth, B.J., Tonkin, C.J. et al. (2004) Metabolic maps and functions of the Plasmodium falciparum apicoplast. Nature Reviews Microbiology, 2, 203-216.
34. Ramya, T.N., Karmodiya, K., Surolia, A. and Surolia, N. (2007) 15-deoxyspergualin primarily targets the trafficking of apicoplast proteins in Plasmodium falciparum. The Journal of Biological Chemistry, 282, 6388-6397.
35. Sommer, M.S., Gould, S.B., Lehmann, P., Gruber, A., Przyborski, J.M. and Maier, U.G. (2007) Der1-mediated preprotein import into the periplastid compartment of chromalveolates? Molecular Biology and Evolution, 24, 918-928.
36. McConkey, G.A., Pinney, J.W., Westhead, D.R., Plueckhahn, K., Fitzpatrick, T.B., Macheroux, P. and Kappes, B. (2004) Annotating the Plasmodium genome and the enigma of the shikimate pathway. Trends in Parasitology, 20, 60-65.
37. Padmanaban, G., Nagaraj, V.A. and Rangarajan, P.N. (2007) An alternative model for heme biosynthesis in the malarial parasite. Trends in Biochemical Sciences, 32, 443-449.
38. Karnataki, A., Derocher, A., Coppens, I., Nash, C., Feagin, J.E. and Parsons, M. (2007) Cell cycle-regulated vesicular trafficking of Toxoplasma APT1, a protein localized to multiple apicoplast membranes. Molecular Microbiology, 63, 1653-1668.
39. Fleige, T., Fischer, K., Ferguson, D.J., Gross, U. and Bohne, W. (2007) Carbohydrate metabolism in the Toxoplasma gondii apicoplast: localization ofthree glycolytic isoenzymes, the single pyruvate dehydrogenase complex, and a plastid phosphate translocator. Eukaryotic Cell, 6, 984-996.
40. Mullin, K.A., Lim, L., Ralph, S.A., Spurck, T.P., Handman, E. and McFadden, G.I. (2006) Membrane transporters in the relict plastid of malaria parasites. Proceedings of the National Academy of Sciences of the United States of America, 103, 9572-9577.
41. Barton, D., Nakanishi, K. and Meth-Cohn, O. (1999) Comprehensive Natural Products Chemistry: Isoprenoids IncludingCarotenoids and Steroids, 1stedn, Elsevier, Amsterdam.
42. Hunter, W.N. (2007) The non-mevalonate pathway of isoprenoid precursor biosynthesis. The Journal of Biological Chemistry, 282, 21573-21577.
43. Ling, Y., Li, Z.H., Miranda, K., Oldfield, E. and Moreno, S.N. (2007) The farnesyl-diphosphate/geranylgeranyl-diphosphate synthase of Toxoplasma gondii is a bifunctional enzyme and a molecular target of bisphosphonates. The Journal of Biological Chemistry, 282, 30804-30816.
44. Ghosh, S., Chan, J.M., Lea, C.R., Meints, G.A., Lewis, J.C., Tovian, Z.S., Flessner, R.M. et al. (2004) Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium species in vitro and in vivo. Journal of Medicinal Chemistry, 47, 175-187.
45. Moreno, S.N.J. and Li, Z.-H. (2008) Anti-infectives targeting the isoprenoid pathway of Toxoplasma gondii. Expert Opinion on Therapeutic Targets, 12, 253-263.
46. Martin, M., Grimley, J. and Lewis, J. (2001) Bisphosphonates inhibit the growth of Trypanosoma brucei, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: a potential route to chemotherapy. Journal of Medicinal Chemistry, 44, 909-916.
47. Mueller, C., Schwender, J., Zeidler, J. and Lichtenthaler, H. (2000) Properties and inhibition of the first two enzymes of the non-mevalonate pathway of isoprenoid biosynthesis. Biochemical Society Transactions, 28, 792-793.
48. Jomaa, H., Wiesner, J., Sanderbrand, S., Altincicek, B., Weidemeyer, C., Hintz, M., Turbachova, I. et al. (1999) Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science, 285, 1573-1576.
49. Wiesner, J. and Jomaa, H. (2007) Isoprenoid biosynthesis of the apicoplast as drug target. Current Drug Targets, 8, 3-13.
50. Müller, C. (2003) Investigations on two enzymes of the plastidic isoprenoid biosynthesis: DOXP-synthase and DOXP-reductoisomerase. Karlsruher Beiträge zur Pflanzenphysiologie, 39, 1-129.
51. Muller, S. and Kappes, B. (2007) Vitamin and cofactor biosynthesis pathways in Plasmodium and other apicomplexan parasites. Trends in Parasitology, 23, 112-121.
52. Leon, A., Liu, L., Yang, Y., Hudock, M.P., Hall, P., Yin, F., Studer, D. et al. (2006) Isoprenoid biosynthesis as a drug target: bisphosphonate inhibition of Escherichia coli K12 growth and synergistic effects of fosmidomycin. Journal of Medicinal Chemistry, 49, 7331-7341.
53. Eastman, R.T., White, J., Hucke, O., Bauer, K., Yokoyama, K., Nallan, L., Chakrabarti, D. et al. (2005) Resistance to a protein farnesyltransferase inhibitor in Plasmodium falciparum. The Journal of Biological Chemistry, 280, 13554-13559.
54. Wiesner, J., Kettler, K., Sakowski, J., Ortmann, R., Katzin, A.M., Kimura, E.A., Silber, K. et al. (2004) Farnesyltransferase inhibitors inhibit the growth of malaria parasites in vitro and in vivo. Angewandte Chemie (International Edition in English), 43, 251-254.
55. Buckner, F.S., Eastman, R.T., Yokoyama, K., Gelb, M.H. and Van Voorhis, W.C. (2005) Protein farnesyl transferase inhibitors for the treatment of malaria and African trypanosomiasis. Current Opinion in Investigational Drugs, 6, 791-797.
56. Nallan, L., Bauer, K.D., Bendale, P., Rivas, K., Yokoyama, K., Horney, C.P., Pendyala, P.R. et al. (2005) Protein farnesyltransferase inhibitors exhibit potent antimalarial activity. Journal of Medicinal Chemistry, 48, 3704-3713.
57. Bendale, P., Olepu, S., Suryadevara, P.K., Bulbule, V., Rivas, K., Nallan, L., Smart, B. et al. (2007) Second generation tetrahydroquinoline-based protein farnesyltransferase inhibitors as antimalarials. Journal of Medicinal Chemistry, 50, 4585-4605.
58. Van Voorhis, W.C., Rivas, K.L., Bendale, P., Nallan, L., Horney, C., Barrett, L.K., Bauer, K.D. et al. (2007) Efficacy, pharmacokinetics, and metabolism of tetrahydroquinoline inhibitors of Plasmodium falciparum protein farnesyltransferase. Antimicrobial Agents and Chemotherapy, 51, 3659-3671.
59. WHO (2007) Medicines for Malaria Venture, Annual Report 2006. WHO, Geneva.
60. Mazumdar, J. and Striepen, B. (2007) Make it or take it: fatty acid metabolism of apicomplexan parasites. Eukaryotic Cell, 6, 1727-1735.
61. Goodman, C.D. and McFadden, G.I. (2007) Fatty acid biosynthesis as a drug target in apicomplexan parasites. Current Drug Targets, 8, 15-30.
62. Waller, R.F., Keeling, P.J., Donald, R.G., Striepen, B., Handman, E., Lang-Unnasch, N., Cowman, A.F.et al. (1998) Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and Plasmodium falciparum. Proceedings of the National Academy of Sciences of the United States of America, 95, 12352-12357.
63. Wright, H.T. and Reynolds, K.A. (2007) Antibacterial targets in fatty acid biosynthesis. Current Opinion in Microbiology, 10, 447-453.
64. McLeod, R., Muench, S.P., Rafferty, J.B., Kyle, D.E., Mui, E.J., Kirisits, M.J., Mack, D.G. et al. (2001) Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of apicomplexan Fab I. International Journal for Parasitology, 31, 109-113.
65. Surolia, N. and Surolia, A. (2001) Triclosan offers protection against blood stages of malaria by inhibiting enoyl-ACP reductase of Plasmodium falciparum. Nature Medicine, 7, 167-173.
66. Nicola, G., Smith, C.A., Lucumi, E., Kuo, M.R., Karagyozov, L., Fidock, D.A., Sacchettini, J.C. et al. (2007) Discovery of novel inhibitors targeting enoyl-acyl carrier protein reductase in Plasmodium falciparum by structure-based virtual screening. Biochemical and Biophysical Research Communications, 358, 686-691.
67. Freundlich, J.S., Wang, F., Tsai, H.C., Kuo, M., Shieh, H.M., Anderson, J.W., Nkrumah, L.J. et al. (2007) X-ray structural analysis of Plasmodium falciparum enoyl acyl carrier protein reductase as a pathway toward the optimization of triclosan antimalarial efficacy. The Journal of Biological Chemistry, 282, 25436-25444.
68. Freundlich, J.S., Yu, M., Lucumi, E., Kuo, M., Tsai, H.C., Valderramos, J.C., Karagyozov, L. et al. (2006) Synthesis and biological activity of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. Part 2: 2'-substituted triclosan derivatives. Bioorganic & Medicinal Chemistry Letters, 16, 2163-2169.
69. Kumar, G., Parasuraman, P., Sharma, S.K., Banerjee, T., Karmodiya, K., Surolia, N. and Surolia, A. (2007) Discovery of a rhodanine class of compounds as inhibitors of Plasmodium falciparum enoyl-acyl carrier protein reductase. Journal of Medicinal Chemistry, 50, 2665-2675.
70. Mishra, S., Karmodiya, K., Parasuraman, P., Surolia, A. and Surolia, N. (2008) Design, synthesis, and application of novel triclosan prodrugs as potential antimalarial and antibacterial agents. Bioorganic and Medicinal Chemistry, 6, 5536-5546.
71. Tarun, A.S., Peng, X., Dumpit, R.F., Ogata, Y., Silva-Rivera, H., Camargo, N., Daly, T.M. et al. (2008) A combined transcriptome and proteome survey of malaria parasite liver stages. Proceedings of the National Academy of Sciences of the United States of America, 105, 305-310.
72. Zhou, Y., Ramachandran, V., Kumar, K.A., Westenberger, S., Refour, P., Zhou, B., Li, F. et al. (2008) Evidence-based annotation of the malaria parasite's genome using comparative expression profiling. PLoS ONE, 3, e1570.
73. Daily, J.P., Scanfeld, D., Pochet, N., Le Roch, K., Plouffe, D., Kamal, M., Sarr, O. et al. (2007) Distinct physiological states of Plasmodium falciparum in malaria-infected patients. Nature, 450, 1091-1095.
74. Cronan, J.E., Zhao, X. and Jiang, Y. (2005) Function, attachment and synthesis of lipoic acid in Escherichia coli. Advances in Microbial Physiology, 50, 103-146.
75. Perham, R.N. (2000) Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annual Review of Biochemistry, 69, 961-1004.
76. Witkowski, A., Joshi, A.K. and Smith, S. (2007) Coupling of the de novo fatty acid biosynthesis and lipoylation pathways in mammalian mitochondria. The Journal of Biological Chemistry, 282, 14178-14185.
77. Liu, B., Wang, Y., Fillgrove, K.L. and Anderson, V.E. (2002) Triclosan inhibits enoyl-reductase of type I fatty acid synthase in vitro andiscytotoxictoMCF-7 and SKBr-3 breast cancer cells. Cancer Chemotherapy and Pharmacology, 49, 187-193.
78. Crawford, M.J., Thomsen-Zieger, N., Ray, M., Schachtner, J., Roos, D.S. and Seeber, F. (2006) Toxoplasma gondii scavenges host-derived lipoic acid despite its de novo synthesis in the apicoplast. The EMBO Journal, 25, 3214-3222.
79. Allary, M., Lu, J.Z., Zhu, L. and Prigge, S.T. (2007) Scavenging of the cofactor lipoate is essential for the survival of the malaria parasite Plasmodium falciparum. Molecular Microbiology, 63, 1331-1344.
80. Mazumdar, J., Wilson, E.H., Masek, K., Hunter, C.A. and Striepen, B., (2006) Apicoplast fatty acid synthesis is essential for organelle biogenesis and parasite survival in Toxoplasma gondii. Proceedings of the National Academy of Sciences of the United States of America, 103, 13192-13197.
81. Pandini, V., Caprini, G., Thomsen, N., Aliverti, A., Seeber, F. and Zanetti, G. (2002) Ferredoxin-NADP + reductase and ferredoxin of the protozoan parasite Toxoplasma gondii interact productively in vitro and in vivo. The Journal of Biological Chemistry, 277, 48463-48471.
82. Rochrich, R.C., Englert, N., Troschke, K., Reichenberg, A., Hintz, M., Seeber, F., Balconi, E. et al. (2005) Reconstitution of an apicoplast-localised electron transfer pathway involved in the isoprenoid biosyntheis of Plasmodium falciparum. FEBS Letters, 579, 6433-6438.
83. Okada, K. and Hase, T. (2005) Cyanobacterial non-mevalonate pathway: (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase interacts with ferredoxin in Thermosynechococcus elongatus BP-1. The Journal of Biological Chemistry, 280, 20672-20679.
84. Seemann, M., Tse Sum Bui, B., Wolff, M., Miginiac-Maslow, M. and Rohmer, M. (2006) Isoprenoid biosynthesis in plant chloroplasts via the MEP pathway: direct thylakoid/ferredoxin-dependent photoreduction of GcpE/IspG. FEBS Letters, 580, 1547-1552.
85. Wang, S.C. and Frey, P.A. (2007) S-adenosylmethionine as an oxidant: the radical SAM superfamily. Trends in Biochemical Sciences, 32, 101-110.
86. Seeber, F. (2002) Biogenesis ofiron-sulfur clusters in amitochondriate and apicomplexan protists. International Journal for Parasitology, 32, 1207-1217.
87. Pilon, M., Abdel-Ghany, S.E., Van Hoewyk, D., Ye, H. and Pilon-Smits, E.A. (2006) Biogenesis of iron-sulfur cluster proteins in plastids. Genetic Engineering (New York), 27, 101-117.
88. +-reductase/ferredoxin redox system as a possible drug target against apicomplexan human parasites. Current Pharmaceutical Design, 11, 3159-3172.
89. Kimata-Ariga, Y., Kurisu, G., Kusunoki, M., Aoki, S., Sato, D., Kobayashi, T., Kita, K. et al. (2007) Cloning and characterization of ferredoxin and ferredoxin-NADP + reductase from human malaria parasite. Journal of Biochemistry, 141, 421-428.
90. Milani, M., Balconi, E., Aliverti, A., Mastrangelo, E., Seeber, F., Bolognesi, M. and Zanetti, G. (2007) Ferredoxin-NADP (+) reductase from Plasmodium falciparum undergoes NADP( +)-dependent dimerization and inactivation: Functional and crystallographic analysis. Journal of Molecular Biology, 367, 501-513.
91. Fletcher, S. and Hamilton, A.D. (2007) Protein-protein interaction inhibitors: small molecules from screening techniques. Current Topics in Medicinal Chemistry, 7, 922-927.
92. Fry, D.C. (2006) Protein-protein interactions as targets for small molecule drug discovery. Biopolymers, 84, 535-552.
93. Weigelt, J., McBroom-Cerajewski, L.D.B., Schapira, M., Zhao, Y. and Arrowmsmith, C.H. (2008) Structural genomics and drug discovery: all in the family. Current Opinion in Chemical Biology, 12, 32-39.
94. Sleno, L. and Emili, A. (2008) Proteomic methods for drug target discovery. Current Opinion in Chemical Biology, 12, 46-54.
95. Shyur, L.-F. and Yang, N.-S. (2008) Metabolomics for phytomedicine research and drug development. Current Opinion in Chemical Biology, 12, 66-71.
96. Baniecki, M.L., Wirth, D.F. and Clardy, J. (2007) High-throughput Plasmodium falciparum growth assay for malaria drug discovery. Antimicrobial Agents and Chemotherapy, 51, 716-723.
97. Smilkstein, M., Sriwilaijaroen, N., Kelly, J.X., Wilairat, P. and Riscoe, M. (2004) Simple and inexpensive fluorescence-based technique for high-throughput antimalarial drug screening. Antimicrobial Agents and Chemotherapy, 48, 1803-1806.
98. Vedadi, M., Lew, J., Artz, J., Amani, M., Zhao, Y., Dong, A., Wasney, G.A. et al. (2007) Genome-scale protein expression and structural biology of Plasmodium falciparum and related Apicomplexan organisms. Molecular and Biochemical Parasitology, 151, 100-110.
99. Mehlin, C., Boni, E., Buckner, F.S., Engel, L., Feist, T., Gelb, M.H., Haji, L. et al. (2006) Heterologous expression of proteins from Plasmodium falciparum: results from 1000 genes. Molecular and Biochemical Parasitology, 148, 144-160.
100. Weisman, J.L., Liou, A.P., Shelat, A.A., Cohen, F.E., Guy, R.K. and DeRisi, J.L. (2006) Searching for new antimalarial therapeutics amongst known drugs. Chemical Biology and Drug Design, 67, 409-416.
101. Leroy, D. and Doerig, C. (2008) Drugging the Plasmodium kinome: the benefits of academia-industry synergy. Trends in Pharmacological Sciences, 29, 241-249.
102. Wang, Y., Utzinger, J., Saric, J., Li, J.V., Burckhardt, J., Dirnhofer, S., Nicholson, J.K.et al. (2008) Global metabolic responses of mice to Trypanosoma brucei brucei infection. Proceedings of the National Academy of Sciences of the United States of America, 105, 6127-6132.
103. Kaddurah-Daouk, R., Kristal, B.S. and Weinshilboum, R.M. (2008) Metabolomics: a global biochemical approach to drug response and disease. Annual Review of Pharmacology and Toxicology, 48, 653-683.
104. Sriram, G., Martinez, J.A., McCabe, E.R.B., Liao, J.C. and Dipple, K.M. (2005) Single-gene disorders: what role could moonlighting enzymes play? American Journal of Human Genetics, 76, 911-924.
105. Copley, S.D. (2003) Enzymes with extra talents: moonlighting functions and catalytic promiscuity. Current Opinion in Chemical Biology, 7, 265-272.
106. Buscaglia, C.A., Coppens, I., Hol, W.G.J. and Nussenzweig, V. (2003) Sites of interaction between aldolase and thrombospondin-related anonymous protein in Plasmodium. Molecular Biology of the Cell, 14, 4947-4957.
107. Jewett, T.J. and Sibley, L.D. (2003) Aldolase forms a bridge between cell surface adhesins and the actin cytoskeleton in apicomplexan parasites. Molecular Cell, 11, 885-894.
108. Ferguson, D.J.P., Parmley, S.F. and Tomavo, S. (2002) Evidence for nuclear localisation of two stage-specific isoenzymes of enolase in Toxoplasma gondii correlates with active parasite replication. International Journal for Parasitology, 32, 1399-1410.
109. Pal-Bhowmick, I., Vora, H.K. and Jarori, G.K. (2007) Sub-cellular localization and post-translational modifications of the Plasmodium yoelii enolase suggest moonlighting functions. Malaria Journal, 6, 45.
110. van Dooren, G.G., Stimmler, L.M. and McFadden, G.I. (2006) Metabolic maps and functions of the Plasmodium mitochondrion. FEMS Microbiology Reviews, 30, 596-630.
111. Rosenthal, P.J. (2001) Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New Directions in Drug Discovery, Humana Press, Totowa.
112. Burkhardt, D., Wiesner, J., Stoesser, N., Ramharter, M., Uhlemann, A.C., Issifou, S., Jomaa, H. et al. (2007) Delayed parasite elimination in human infections treated with clindamycin parallels "delayed death" of Plasmodium falciparum in vitro. International Journal for Parasitology, 37, 777-785.
113. Wishart, D.S., Knox, C., Guo, A.C., Cheng, D., Shrivastava, S., Tzur, D., Gautam, B. et al. (2008) DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Research, 36, D901-D906.