Genetic validation of aminoacyl-tRNA synthetases as drug targets in Trypanosoma brucei

Eukaryotic Cell

Volumn 13, Issue 4, 2014, Pages 504-516

  Kalidas, Savitha ^a   Cestari, Igor ^b   Monnerat, Severine ^a   Li, Qiong ^a   Regmi, Sandesh ^a   Hasle, Nicholas ^a   Labaied, Mehdi ^b   Parsons, Marilyn ^b   Stuart, Kenneth ^b   Phillips, Margaret A ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b SEATTLE BIOMEDICAL RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID TRANSFER RNA LIGASE; ANTITRYPANOSOMAL AGENT; BORRELIDIN; FATTY ALCOHOL; MESSENGER RNA; PROTOZOAL PROTEIN; SMALL INTERFERING RNA;

ARTICLE; CELL CYCLE; CYTOSOL; DRUG ANTAGONISM; DRUG DEVELOPMENT; DRUG EFFECT; ENZYMOLOGY; GENE EXPRESSION REGULATION; GENE SILENCING; GENETICS; METABOLISM; MITOCHONDRION; SIGNAL TRANSDUCTION; TRYPANOSOMA BRUCEI; VALIDATION STUDY;

AMINO ACYL-TRNA SYNTHETASES; CELL CYCLE; CYTOSOL; DRUG DISCOVERY; FATTY ALCOHOLS; GENE EXPRESSION REGULATION; GENE KNOCKDOWN TECHNIQUES; MITOCHONDRIA; PROTOZOAN PROTEINS; RNA, MESSENGER; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; TRYPANOCIDAL AGENTS; TRYPANOSOMA BRUCEI BRUCEI;

EID: 84897402075     PISSN: 15359778     EISSN: None     Source Type: Journal    
DOI: 10.1128/EC.00017-14     Document Type: Article

References (78)

1. Kennedy PG. 2013. Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness). Lancet Neurol. 12:186-194. http://dx.doi.org/10.1016/S1474-4422(12)70296-X.
2. Stuart K, Brun R, Croft S, Fairlamb A, Gurtler RE, McKerrow J, Reed S, Tarleton R. 2008. Kinetoplastids: related protozoan pathogens, different diseases. J. Clin. Invest. 118:1301-1310. http://dx.doi.org/10.1172 /JCI33945.
3. Jacobs RT, Nare B, Phillips MA. 2011. State of the art in African trypanosome drug discovery. Curr. Top. Med. Chem. 11:1255-1274. http://dx.doi. org/10.2174/156802611795429167.
4. Yun O, Priotto G, Tong J, Flevaud L, Chappuis F. 2010. NECT is next: implementing the new drug combination therapy for Trypanosoma brucei gambiense sleeping sickness. PLoS Negl. Trop. Dis. 4:e720. http://dx. doi.org/10.1371/journal.pntd.0000720.
5. Frearson JA, Wyatt PG, Gilbert IH, Fairlamb AH. 2007. Target assessment for antiparasitic drug discovery. Trends Parasitol. 23:589-595. http: //dx.doi.org/10.1016/j.pt.2007.08.019.
6. Brun R, Don R, Jacobs RT, Wang MZ, Barrett MP. 2011. Development of novel drugs for human African trypanosomiasis. Future Microbiol. 6:677-691. http://dx.doi.org/10.2217/fmb.11.44.
7. Agüero F, Al-Lazikani B, Aslett M, Berriman M, Buckner FS, Campbell RK, Carmona S, Carruthers IM, Chan AW, Chen F, Crowther GJ, Doyle MA, Hertz-Fowler C, Hopkins AL, McAllister G, Nwaka S, Overington JP, Pain A, Paolini GV, Pieper U, Ralph SA, Riechers A, Roos DS, Sali A, Shanmugam D, Suzuki T, Van Voorhis WC, Verlinde CL. 2008. Genomic-scale prioritization of drug targets: the TDR Targets database. Nat. Rev. Drug Discov. 7:900-907. http://dx.doi.org/10.1038 /nrd2684.
8. Magariños MP, Carmona SJ, Crowther GJ, Ralph SA, Roos DS, Shanmugam D, Van Voorhis WC, Agüero F. 2012. TDR Targets: a chemogenomics resource for neglected diseases. Nucleic Acids Res. 40:D1118-D1127. http://dx.doi.org/10.1093/nar/gkr1053.
9. Hopkins AL, Groom CR. 2002. The druggable genome. Nat. Rev. Drug Discov. 1:727-730. http://dx.doi.org/10.1038/nrd892.
10. Baquero F, Blazquez J. 1997. Evolution of antibiotic resistance. Trends Ecol. Evol. 12:482-487. http://dx.doi.org/10.1016/S0169-5347(97)01223-8.
11. Gadakh B, Van Aerschot A. 2012. Aminoacyl-tRNA synthetase inhibitors as antimicrobial agents: a patent review from 2006 till present. Expert Opin. Ther. Pat. 22:1453-1465. http://dx.doi.org/10.1517/13543776.2012. 732571.
12. Vondenhoff GH, Van Aerschot A. 2011. Aminoacyl-tRNA synthetase inhibitors as potential antibiotics. Eur. J. Med. Chem. 46:5227-5236. http: //dx.doi.org/10.1016/j.ejmech.2011.08.049.
13. Niemann M, Schneider A, Cristodero M. 2011. Mitochondrial translation in trypanosomatids: a novel target for chemotherapy? Trends Parasitol. 27:429-433. http://dx.doi.org/10.1016/j.pt.2011.03.011.
14. WilsonDN. 2009. TheA-Zof bacterial translation inhibitors. Crit. Rev. Biochem. Mol. Biol. 44:393-433. http://dx.doi.org/10.3109/10409230903307311.
15. Perona JJ, Hadd A. 2012. Structural diversity and protein engineering of the aminoacyl-tRNA synthetases. Biochemistry 51:8705-8729. http://dx. doi.org/10.1021/bi301180x.
16. Delarue M. 1995. Partition of aminoacyl-tRNA synthetases in two different structural classes dating back to early metabolism: implications for the origin of the genetic code and the nature of protein sequences. J. Mol. Evol. 41:703-711.
17. Nagel GM, Doolittle RF. 1991. Evolution and relatedness in two aminoacyl-tRNA synthetase families. Proc. Natl. Acad. Sci. U. S. A. 88:8121-8125. http://dx.doi.org/10.1073/pnas.88.18.8121.
18. O'Donoghue P, Luthey-Schulten Z. 2003. On the evolution of structure in aminoacyl-tRNA synthetases. Microbiol. Mol. Biol. Rev. 67:550-573. http://dx.doi.org/10.1128/MMBR.67.4.550-573.2003.
19. Hoepfner D, McNamara CW, Lim CS, Studer C, Riedl R, Aust T, McCormack SL, Plouffe DM, Meister S, Schuierer S, Plikat U, Hartmann N, Staedtler F, Cotesta S, Schmitt EK, Petersen F, Supek F, Glynne RJ, Tallarico JA, Porter JA, Fishman MC, Bodenreider C, Diagana TT, Movva NR, Winzeler EA. 2012. Selective and specific inhibition of the Plasmodium falciparum lysyl-tRNA synthetase by the fungal secondary metabolite cladosporin. Cell Host Microbe 11:654-663. http: //dx.doi.org/10.1016/j.chom.2012.04.015.
20. Gowri VS, Ghosh I, Sharma A, Madhubala R. 2012. Unusual domain architecture of aminoacyl tRNA synthetases and their paralogs from Leishmania major. BMCGenomics 13:621. http://dx.doi.org/10.1186/1471-2164-13-621.
21. Cestari I, Kalidas S, Monnerat S, Anupama A, Phillips MA, Stuart K. 2013. A multiple aminoacyl-tRNA synthetase complex that enhances tRNA-aminoacylation in African trypanosomes. Mol. Cell. Biol. 33:4872-4888. http://dx.doi.org/10.1128/MCB.00711-13.
22. Alfonzo JD, Soll D. 2009. Mitochondrial tRNA import-the challenge to understand has just begun. Biol. Chem. 390:717-722. http://dx.doi.org/10. 1515/BC.2009.101.
23. Tschopp F, Charriere F, Schneider A. 2011. In vivo study in Trypanosoma brucei links mitochondrial transfer RNA import to mitochondrial protein import. EMBO Rep. 12:825-832. http://dx.doi.org/10.1038 /embor.2011.111.
24. Español Y, Thut D, Schneider A, Ribas de Pouplana L. 2009. A mechanism for functional segregation of mitochondrial and cytosolic genetic codes. Proc. Natl. Acad. Sci. U. S. A. 106:19420-19425. http://dx.doi.org /10.1073/pnas.0909937106.
25. Charrière F, O'Donoghue P, Helgadóttir S, Maréchal-Drouard L, Cristodero M, Horn EK, Söll D, Schneider A 2009. Dual targeting of a tRNAAsp requires two different aspartyl-tRNA synthetases in Trypanosoma brucei. J. Biol. Chem. 284:16210-16217. http://dx.doi.org/10.1074 /jbc.M109.005348.
26. Charrière F, Helgadóttir S, Horn EK, Söll D, Schneider A. 2006. Dual targeting of a single tRNA(Trp) requires two different tryptophanyl-tRNA synthetases in Trypanosoma brucei. Proc. Natl. Acad. Sci. U. S. A. 103: 6847-6852. http://dx.doi.org/10.1073/pnas.0602362103.
27. Cristodero M, Seebeck T, Schneider A. 2010. Mitochondrial translation is essential in bloodstream forms of Trypanosoma brucei. Mol. Microbiol. 78:757-769. http://dx.doi.org/10.1111/j.1365-2958.2010.07368.x.
28. Rinehart J, Horn EK, Wei D, Soll D, Schneider A. 2004. Non-canonical eukaryotic glutaminyl-and glutamyl-tRNA synthetases form mitochondrial aminoacyl-tRNA in Trypanosoma brucei. J. Biol. Chem. 279:1161-1166. http://dx.doi.org/10.1074/jbc.M310100200.
29. Rettig J, Wang Y, Schneider A, Ochsenreiter T. 2012. Dual targeting of isoleucyl-tRNA synthetase in Trypanosoma brucei is mediated through alternative trans-splicing. Nucleic Acids Res. 40:1299-1306. http://dx.doi. org/10.1093/nar/gkr794.
30. Cestari I, Stuart K. 2013. Inhibition of isoleucyl-tRNA synthetase as a potential treatment for human African trypanosomiasis. J. Biol. Chem. 288:14256-14263. http://dx.doi.org/10.1074/jbc.M112.447441.
31. Zhao Y, Wang Q, Meng Q, Ding D, Yang H, Gao G, Li D, Zhu W, Zhou H. 2012. Identification of Trypanosoma brucei leucyl-tRNA synthetase inhibitors by pharmacophore-and docking-based virtual screening and synthesis. Bioorg. Med. Chem. 20:1240-1250. http://dx.doi.org/10.1016/j. bmc.2011.12.035.
32. Ding D, Meng Q, Gao G, Zhao Y, Wang Q, Nare B, Jacobs R, Rock F, Alley MR, Plattner JJ, Chen G, Li D, Zhou H. 2011. Design, synthesis, and structure-activity relationship of Trypanosoma brucei leucyl-tRNA synthetase inhibitors as antitrypanosomal agents. J. Med. Chem. 54:1276-1287. http://dx.doi.org/10.1021/jm101225g.
33. Shibata S, Gillespie JR, Kelley AM, Napuli AJ, Zhang Z, Kovzun KV, Pefley RM, Lam J, Zucker FH, Van Voorhis WC, Merritt EA, Hol WG, Verlinde CL, Fan E, Buckner FS. 2011. Selective inhibitors of methionyltRNA synthetase have potent activity against Trypanosoma brucei infection in mice. Antimicrob. Agents Chemother. 55:1982-1989. http://dx.doi. org/10.1128/AAC.01796-10.
34. Koh CY, Kim JE, Shibata S, Ranade RM, Yu M, Liu J, Gillespie JR, Buckner FS, Verlinde CL, Fan E, Hol WG. 2012. Distinct states of methionyl-tRNA synthetase indicate inhibitor binding by conformational selection. Structure 20:1681-1691. http://dx.doi.org/10.1016/j.str.2012. 07.011.
35. Shibata S, Gillespie JR, Ranade RM, Koh CY, Kim JE, Laydbak JU, Zucker FH, Hol WG, Verlinde CL, Buckner FS, Fan E. 2012. Urea-based inhibitors of Trypanosoma brucei methionyl-tRNA synthetase: selectivity and in vivo characterization. J. Med. Chem. 55:6342-6351. http://dx.doi. org/10.1021/jm300303e.
36. Merritt EA, Arakaki TL, Gillespie JR, Larson ET, Kelley A, Mueller N, Napuli AJ, Kim J, Zhang L, Verlinde CL, Fan E, Zucker F, Buckner FS, van Voorhis WC, Hol WG. 2010. Crystal structures of trypanosomal histidyl-tRNA synthetase illuminate differences between eukaryotic and prokaryotic homologs. J. Mol. Biol. 397:481-494. http://dx.doi.org/10. 1016/j.jmb.2010.01.051.
37. Merritt EA, Arakaki TL, Gillespie R, Napuli AJ, Kim JE, Buckner FS, Van Voorhis WC, Verlinde CL, Fan E, Zucker F, Hol WG. 2011. Crystal structures of three protozoan homologs of tryptophanyl-tRNA synthetase. Mol. Biochem. Parasitol. 177:20-28. http://dx.doi.org/10.1016/j. molbiopara.2011.01.003.
38. Willert EK, Phillips MA. 2008. Regulated expression of an essential allosteric activator of polyamine biosynthesis in African trypanosomes. PLoS Pathog. 4:e1000183. http://dx.doi.org/10.1371/journal.ppat.1000183.
39. Kalidas S, Li Q, Phillips MA. 2011. A Gateway(R) compatible vector for gene silencing in bloodstream form Trypanosoma brucei. Mol. Biochem. Parasitol. 178:51-55. http://dx.doi.org/10.1016/j.molbiopara.2011.03.002.
40. Brun R, Schonenberger M. 1979. Cultivation and in vitro cloning or procyclic culture forms of Trypanosoma brucei in a semi-defined medium. Acta Trop. 36:289-292.
41. Redmond S, Vadivelu J, Field MC. 2003. RNAit: an automated web-based tool for the selection ofRNAitargets inTrypanosomabrucei. Mol. Biochem. Parasitol. 128:115-118. http://dx.doi.org/10.1016/S0166-6851(03)00045-8.
42. Inoue M, Nakamura Y, Yasuda K, Yasaka N, Hara T, Schnaufer A, Stuart K, Fukuma T. 2005. The 14-3-3 proteins of Trypanosoma brucei function in motility, cytokinesis, and cell cycle. J. Biol. Chem. 280:14085-14096. http://dx.doi.org/10.1074/jbc.M412336200.
43. Wirtz E, Leal S, Ochatt C, Cross G. 1999. A tightly regulated inducible expression system for conditional gene knock-outs and dominantnegative genetics in T. brucei. Mol. Biochem. Parasitol. 99:89-101. http: //dx.doi.org/10.1016/S0166-6851(99)00002-X.
44. Schnaufer A, Panigrahi AK, Panicucci B, Igo RP, Jr, Wirtz E, Salavati R, Stuart K. 2001. An RNA ligase essential for RNA editing and survival of the bloodstream form of Trypanosoma brucei. Science 291:2159-2162. http://dx.doi.org/10.1126/science.1058655.
45. Brenndörfer M, Boshart M. 2010. Selection of reference genes for mRNA quantification in Trypanosoma brucei. Mol. Biochem. Parasitol. 172:52-55. http://dx.doi.org/10.1016/j.molbiopara.2010.03.007.
46. Winer J, Jung CK, Shackel I, Williams PM. 1999. Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro. Anal. Biochem. 270:41-49. http://dx.doi.org/10.1006/abio.1999.4085.
47. Tu X, Wang CC. 2004. The involvement of two cdc2-related kinases (CRKs) in Trypanosoma brucei cell cycle regulation and the distinctive stage-specific phenotypes caused by CRK3 depletion. J. Biol. Chem. 279: 20519-20528. http://dx.doi.org/10.1074/jbc.M312862200.
48. Tu X, Wang CC. 2005. Coupling of posterior cytoskeletal morphogenesis to the G1/S transition in the Trypanosoma brucei cell cycle. Mol. Biol. Cell 16:97-105. http://dx.doi.org/10.1091/mbc.E04-05-0368.
49. Carnes J, Schnaufer A, McDermott SM, Domingo G, Proff R, Steinberg AG, Kurtz I, Stuart K. 2012. Mutational analysis of Trypanosoma brucei editosome proteins KREPB4 and KREPB5 reveals domains critical for function. RNA 18:1897-1909. http://dx.doi.org/10.1261/rna.035048.112.
50. Cestari I, Stuart K. 2013. A spectrophotometric assay for quantitative measurement of aminoacyl-tRNA synthetase activity. J. Biomol. Screen. 18:490-497. http://dx.doi.org/10.1177/1087057112465980.
51. Panigrahi AK, Ogata Y, Zikova A, Anupama A, Dalley RA, Acestor N, Myler PJ, Stuart KD. 2009. A comprehensive analysis of Trypanosoma brucei mitochondrial proteome. Proteomics 9:434-450. http://dx.doi.org /10.1002/pmic.200800477.
52. Ling J, Peterson KM, Simonovic I, Cho C, Soll D, Simonovic M. 2012. Yeast mitochondrial threonyl-tRNA synthetase recognizes tRNA isoacceptors by distinct mechanisms and promotes CUN codon reassignment. Proc. Natl. Acad. Sci. U. S. A. 109:3281-3286. http://dx.doi.org/10.1073 /pnas.1200109109.
53. Ruan B, Bovee ML, Sacher M, Stathopoulos C, Poralla K, Francklyn CS, Soll D. 2005. A unique hydrophobic cluster near the active site contributes to differences in borrelidin inhibition among threonyl-tRNA synthetases. J. Biol. Chem. 280:571-577. http://dx.doi.org/10.1074/jbc.M411039200.
54. Jackson KE, Pham JS, Kwek M, De Silva NS, Allen SM, Goodman CD, McFadden GI, de Pouplana LR, Ralph SA. 2012. Dual targeting of aminoacyl-tRNA synthetases to the apicoplast and cytosol in Plasmodium falciparum. Int. J. Parasitol. 42:177-186. http://dx.doi.org/10.1016/j. ijpara.2011.11.008.
55. Gao YM, Wang XJ, Zhang J, Li M, Liu CX, An J, Jiang L, Xiang WS. 2012. Borrelidin, a potent antifungal agent: insight into the antifungal mechanism against Phytophthora sojae. J. Agric. Food Chem. 60:9874-9881. http://dx.doi.org/10.1021/jf302857x.
56. Habibi D, Ogloff N, Jalili RB, Yost A, Weng AP, Ghahary A, Ong CJ. 2012. Borrelidin, a small molecule nitrile-containing macrolide inhibitor of threonyl-tRNA synthetase, is a potent inducer of apoptosis in acute lymphoblastic leukemia. Invest. New Drugs 30:1361-1370. http://dx.doi. org/10.1007/s10637-011-9700-y.
57. Mariner KR, Ooi N, Roebuck D, O'Neill AJ, Chopra I. 2011. Further characterization of Bacillus subtilis antibiotic biosensors and their use for antibacterial mode-of-action studies. Antimicrob. Agents Chemother. 55: 1784-1786. http://dx.doi.org/10.1128/AAC.01710-10.
58. Alsford S, Turner DJ, Obado SO, Sanchez-Flores A, Glover L, Berriman M, Hertz-Fowler C, Horn D. 2011. High-throughput phenotyping using parallel sequencingofRNAinterference targets in the Africantrypanosome. GenomeRes. 21:915-924. http://dx.doi.org/10.1101/gr.115089.110.
59. Tshori S, Razin E, Nechushtan H. 28 March 2013. Amino-acyl tRNA synthetases generate dinucleotide polyphosphates as second messengers: functional implications. Top. Curr. Chem. http://dx.doi.org/10.1007 /128_2013_426.
60. Han JM, Jeong SJ, Park MC, Kim G, Kwon NH, Kim HK, Ha SH, Ryu SH, Kim S. 2012. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell 149:410-424. http://dx.doi. org/10.1016/j.cell.2012.02.044.
61. Ofir-Birin Y, Fang P, Bennett SP, Zhang HM, Wang J, Rachmin I, Shapiro R, Song J, Dagan A, Pozo J, Kim S, Marshall AG, Schimmel P, Yang XL, Nechushtan H, Razin E, Guo M. 2013. Structural switch of lysyl-tRNA synthetase between translation and transcription. Mol. Cell 49:30-42. http://dx.doi.org/10.1016/j.molcel.2012.10.010.
62. Teng M, Hilgers MT, Cunningham ML, Borchardt A, Locke JB, Abraham S, Haley G, Kwan BP, Hall C, Hough GW, Shaw KJ, Finn J. 2013. Identification of bacteria-selective threonyl-tRNA synthetase substrate inhibitors by structure-based design. J. Med. Chem. 56:1748-1760. http: //dx.doi.org/10.1021/jm301756m.
63. Metlitskaya A, Kazakov T, Kommer A, Pavlova O, Praetorius-Ibba M, Ibba M, Krasheninnikov I, Kolb V, Khmel I, Severinov K. 2006. Aspartyl-tRNA synthetase is the target of peptide nucleotide antibiotic Microcin C. J. Biol. Chem. 281: 18033-18042. http://dx.doi.org/10.1074/jbc.M513174200.
64. Balg C, Blais SP, Bernier S, Huot JL, Couture M, Lapointe J, Chenevert R. 2007. Synthesis of beta-ketophosphonate analogs of glutamyl and glutaminyl adenylate, and selective inhibition of the corresponding bacterial aminoacyl-tRNA synthetases. Bioorg. Med. Chem. 15:295-304. http://dx. doi.org/10.1016/j.bmc.2006.09.056.
65. Miyamoto Y, Machida K, Mizunuma M, Emoto Y, Sato N, Miyahara K, Hirata D, Usui T, Takahashi H, Osada H, Miyakawa T. 2002. Identification of Saccharomyces cerevisiae isoleucyl-tRNA synthetase as a target of the G1-specific inhibitor Reveromycin A. J. Biol. Chem. 277:28810-28814. http://dx.doi.org/10.1074/jbc.M203827200.
66. Paulander W, Andersson DI, Maisnier-Patin S. 2010. Amplification of the gene for isoleucyl-tRNA synthetase facilitates adaptation to the fitness cost of mupirocin resistance in Salmonella enterica. Genetics 185:305-312. http://dx.doi.org/10.1534/genetics.109.113514.
67. Petraitis V, Petraitiene R, Kelaher AM, Sarafandi AA, Sein T, Mickiene D, Bacher J, Groll AH, Walsh TJ. 2004. Efficacy of PLD-118, a novel inhibitor of candida isoleucyl-tRNA synthetase, against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant C. albicans. Antimicrob. Agents Chemother. 48:3959-3967. http://dx.doi. org/10.1128/AAC.48.10.3959-3967.2004.
68. Houge-Frydrych CS, Gilpin ML, Skett PW, Tyler JW. 2000. SB-203207 and SB-203208, two novel isoleucyl tRNA synthetase inhibitors from a Streptomyces sp. II. Structure determination. J. Antibiot. (Tokyo) 53: 364-372. http://dx.doi.org/10.7164/antibiotics.53.364.
69. Houge-Frydrych CS, Readshaw SA, Bell DJ. 2000. SB-219383, a novel tyrosyl tRNA synthetase inhibitor from a Micromonospora sp. II. Structure determination. J. Antibiot. (Tokyo) 53:351-356. http://dx.doi.org/10. 7164/antibiotics.53.351.
70. Green LS, Bullard JM, Ribble W, Dean F, Ayers DF, Ochsner UA, Janjic N, Jarvis TC. 2009. Inhibition of methionyl-tRNA synthetase by REP8839 and effects of resistance mutations on enzyme activity. Antimicrob. Agents Chemother. 53:86-94. http://dx.doi.org/10.1128/AAC.00275-08.
71. Roth A, Creppy EE, Kane A, Bacha H, Steyn PS, Roschenthaler R, Dirheimer G. 1989. Influence of ochratoxin B on the ochratoxin A inhibition of phenylalanyl-tRNA formation in vitro and protein synthesis in hepatoma tissue culture cells. Toxicol. Lett. 45:307-313. http://dx.doi.org /10.1016/0378-4274(89)90022-2.
72. Jarvest RL, Erskine SG, Forrest AK, Fosberry AP, Hibbs MJ, Jones JJ, O'Hanlon PJ, Sheppard RJ, Worby A. 2005. Discovery and optimisation of potent, selective, ethanolamine inhibitors of bacterial phenylalanyl tRNA synthetase. Bioorg. Med. Chem. Lett. 15:2305-2309. http://dx.doi. org/10.1016/j.bmcl.2005.03.003.
73. Zhou H, Sun L, Yang XL, Schimmel P. 2013. ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase. Nature 494: 121-124. http://dx.doi.org/10.1038/nature11774.
74. Stefanska AL, Fulston M, Houge-Frydrych CS, Jones JJ, Warr SR. 2000. A potent seryl tRNA synthetase inhibitor SB-217452 isolated from a Streptomyces species. J. Antibiot. (Tokyo) 53:1346-1353. http://dx.doi.org/10. 7164/antibiotics.53.1346.
75. Xiao ZP, Ma TW, Liao ML, Feng YT, Peng XC, Li JL, Li ZP, Wu Y, Luo Q, Deng Y, Liang X, Zhu HL. 2011. Tyrosyl-tRNA synthetase inhibitors as antibacterial agents: synthesis, molecular docking and structureactivity relationship analysis of 3-aryl-4-arylaminofuran-2(5H)-ones. Eur. J. Med. Chem. 46:4904-4914. http://dx.doi.org/10.1016/j.ejmech. 2011.07.047.
76. Greenwood RC, Gentry DR. 2002. Confirmation of the antibacterial mode of action of SB-219383, a novel tyrosyl tRNA synthetase inhibitor from a Micromonospora sp. J. Antibiot. (Tokyo) 55:423-426. http://dx. doi.org/10.7164/antibiotics.55.423.
77. Jakubowski H. 1982. The mechanism of inhibition of valyl-tRNA synthetase by S-adenosylhomocysteine. Biochim. Biophys. Acta 709:325-331. http://dx.doi.org/10.1016/0167-4838(82)90475-7.
78. Siegel TN, Hekstra DR, Wang X, Dewell S, Cross GA. 2010. Genomewide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites. Nucleic Acids Res. 38:4946-4957. http://dx.doi.org/10.1093/nar/gkq237.