跳到主要內容

簡易檢索 / 詳目顯示

回結果列表
研究生： 伊凡緹
Indira Rizqita Ivanesthi
論文名稱： Adaptive tRNA recognition by aminoacyl-tRNA synthetases
指導教授： 王健家
Chien-Chia Wang
徐欣伶
Hsin-ling Hsu
口試委員:
學位類別： 博士
Doctor
系所名稱： 生醫理工學院 - 生命科學系
Department of Life Science
論文出版年： 2025
畢業學年度： 113
語文別： 英文
論文頁數： 97
中文關鍵詞： One keyword per line 、tRNA identity 、prolyl-tRNA synthetase 、histidyl-tRNA synthetase 、tRNA recognition
外文關鍵詞： One keyword per line, tRNA identity, prolyl-tRNA synthetase, histidyl-tRNA synthetase, tRNA recognition
相關次數： 點閱：22  下載：0 
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報

    • Aminoacyl-tRNA synthetase (aaRSs) 是一群參與蛋白質合成的必要酵素，負責辨識並將特定的胺基酸接到其相應的tRNA上，是維持蛋白質轉譯準確性的關鍵步驟。本篇論文探討Histidyl-tRNA synthetases (HisRS) 與Prolyl-tRNA synthetases (ProRS) 在不同生物中如何與tRNA進行共演化，改變其結構以及辨識tRNA的機制以對應非典型tRNA。在一種嗜熱古菌Nanoarchaeum equitans中，由於缺乏RNase P修飾tRNA的5′端，且基因轉錄出的pre-tRNAHis並未帶有前導序列(Leader sequence)，此種古菌的tRNAHis有別於其他物種，帶有5′三磷酸(ppp-tRNA)而非單磷酸。我們發現其HisRS (NeHisRS) 與典型HisRS類似，仍然偏好帶有5′單磷酸 (p-tRNA)的tRNAHis，且重度依靠G-1位點來辨識tRNAHis。特別的是，與典型原核生物HisRS不同，NeHisRS能夠有效地胺醯化帶有A73或C73的tRNAHis，顯示其對辨別tRNAHis的專一性有所放寬。ProRS存在兩種結構形式，分別是原核生物型(P-type)，和真核生物/古菌型(E-type)，通常細菌只會帶有一個P-type ProRS。有趣的是，蘇雲金芽孢桿菌 (Bacillus thuringiensis) 同時帶有這二種ProRS，分別為BtProRS1 (P-type) 與BtProRS2 (E-type)。我們發現，BtProRS1與BtProRS2雖同能識別P-type tRNAPro，但採用不同的識別機制，且BtProRS2對halofuginone (HF)及環境壓力的耐受性更強，顯示帶有第二種ProRS的演化優勢。在弓形蟲 (Toxoplasma gondii)中，單一一種E-type ProRS (TgProRS) 能胺醯化細胞質(E-type)及頂質體(P-type)兩種具有不同識別元素的tRNAPro。TgProRS的motif 2 loop突變會選擇性影響不同tRNA的識別。此外，細胞質tRNAPro對HF的敏感度高於頂質體tRNAPro。這些發現揭示aaRS如何透過不同識別策略因應tRNA多樣性，深化對酵素與tRNA共同演化的理解，並為設計具選擇性的抗微生物療法提供理論依據。

    Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that ensure translational fidelity by specifically recognizing and aminoacylating their cognate tRNAs. This dissertation explores the adaptive recognition mechanisms of histidyl- and prolyl-tRNA synthetases (HisRS and ProRS) in diverse organisms, highlighting structural and functional evolution in response to noncanonical tRNA features. In Nanoarchaeum equitans, which lacks RNase P and transcribes leaderless tRNAs with 5′-triphosphates (ppp-tRNAs), we show that its HisRS (NeHisRS) maintains a strong preference for tRNAHis with a 5′-monophosphate (p-tRNAHis) and relies heavily on G-1 for substrate recognition. Unlike typical prokaryotic HisRSs, NeHisRS charges tRNAHis with A73 or C73 with similar efficiency, indicating relaxed specificity for the discriminator base. ProRSs exist in two structural forms: prokaryotic (P-type) and eukaryotic/archaeal (E-type). In Bacillus thuringiensis, both types coexist. Although BtProRS1 and BtProRS2 recognize the same P-type tRNAPro, they use distinct mechanisms. BtProRS2 also shows greater resistance to hf and stress conditions, suggesting an adaptive advantage. In Toxoplasma gondii, a single E-type ProRS (TgProRS) aminoacylates both cytosolic and apicoplast tRNAPro isoacceptors with distinct identity elements. Mutations in TgProRS’s motif 2 loop selectively impact substrate recognition. Additionally, cytosolic tRNAPro charging is more sensitive to halofuginone than its apicoplast counterpart. These findings reveal how aaRSs evolve distinct recognition strategies to accommodate tRNA diversity, offering insights into enzyme–substrate coevolution and informing strategies for targeted antimicrobial development.

    ABSTRACT v ABSTRACT (in Chinese) vi ACKNOWLEDGEMENT vii LIST OF PUBLICATIONS viii TABLE OF CONTENT ix LIST OF FIGURES xii LIST OF TABLES xiii ABBREVIATION xiv Section I: Nanoarchaeum equitans Histidyl-tRNA synthetase 1 CHAPTER I. Introduction 1 1.1 Aminoacyl-tRNA synthetase are essential for protein synthesis 1 1.2 Histidyl-tRNA synthetase 2 1.3 G-1 is the main identity element in tRNAHis for HisRS recognition 3 1.4 Nanoarchaeum equitants is RNase-P free organism 4 1.5 Specific aim 4 CHAPTER II MATERIALS and METHODS 5 2.1 Construction of plasmids 5 2.2 Complementation assay for cytoplasmic activity 5 2.3 Complementation assay for mitochondrial ProRS activity 6 2.4 Preparation of tRNAHis transcripts 6 CHAPTER III RESULTS 8 3.1 NetRNAHis carries a 5’-triphosphorylated G-1 8 3.2 NeHisRS is a thermophilic enzyme that can efficiently charge tRNAHis with A73 10 3.3 NeHisRS prefers p-tRNAHis over ppp-tRNAHis 11 3.4 The invariant Q residue within motif 2’s loop of NeHisRS is not essential for recognizing tRNAHis 14 3.5 NeHisRS efficiently rescues the mitochondrial defect of a yeast HisRS KO strain 15 CHAPTER IV DISCUSSION 17 4.1 NeHisRS prefers tRNAHis with 5’-monophosphate 17 4.2 C73 is dispensable for recognition of NetRNAHis 17 4.3 G-1 is the primary identity element of NetRNAHis 18 4.4 Coevolution between NetRNAHis and NeHisRS 18 CHAPTER V CONCLUSIONS 19 Section II: Bacillus thuringiensis Prolyl-tRNA synthetase 20 CHAPTER I. Introduction 20 1.1 Prolyl-tRNA synthetase 20 1.2 The identity element tRNAPro and its recognition by ProRS 20 1.3 Bacillus thuringiensis ProRS and its tRNAsPro 21 1.4 Specific aim 21 CHAPTER II MATERIALS and METHODS 23 2.1 Construction of plasmids 23 2.2 Functional Complementation of Yeast PROS1 Deletion 23 2.3 Functional Complementation of Yeast PROS12 Deletion 23 2.4 Reverse-transcription (RT)-PCR 24 2.5 Aminoacylation assay 24 CHAPTER III 26 RESULTS 26 3.1 Constitutive In Vivo Expression of BtProRS1 and BtProRS2 26 3.2 BtProRS1 and BtProRS2 both exhibit specificity toward the P-type tRNAPro 28 3.3 BtProRS1 and BtProRS2 can replace the function of yeast PROS2, but not PROS1. 30 3.4 BtProRS1 and BtProRS2 target the same identity elements in BttRNAPro 31 3.5 BtProRS2 recognizes the identity elements G72 and A73 via a different mechanism 34 3.6 BtProRS2 exhibits greater resistance to HF compared to typical E-type ProRSs 35 3.7 BtProRS2 exhibits a higher tolerance toward stresses than does BtProRS1 36 CHAPTER IV 39 DISCUSSION 39 4.1 BtProRS2 is classified as an E-type enzyme, yet it has evolved to specifically recognize and interact with the P-type tRNAPro 39 4.2 BtProRS2 employs a unique mechanism to recognize G72 and A73 40 4.3 BtProRS2 is much more resistant to HF than a typical E-type ProRS 41 4.4 The acquisition of an E-type ProRS may provide a survival benefit to the bacterium 42 CHAPTER V 44 CONCLUSIONS 44 Section III: Toxoplasma gondii Prolyl-tRNA synthetase 45 CHAPTER I. Introduction 45 1.1 Prolyl-tRNA synthetase 45 1.2 Toxoplasma gondii ProRS and tRNAsPro 46 1.3 Specific aim 47 CHAPTER II MATERIALS and METHODS 48 2.1 Construction plasmids 48 2.2 Heterologous complementation assay for cytoplasmic ProRS activity 48 2.3 Heterologous complementation assay for mitochondrial ProRS activity 48 2.4 Protein purification and Western blotting 49 2.5 tRNAPro preparation and aminoacylation 49 CHAPTER III RESULTS 51 3.1 TgProRS effectively aminoacylates both E- and P-type tRNAPro isoacceptors 51 3.2 TgProRS recognizes distinct features in E- and P-type tRNAPro isoacceptors 53 3.3 The motif 2 loop plays a critical role in the relaxed specificity of TgProRS 54 3.4 TgProRS can functionally substitute for both yeast PROS1 and PROS2 56 3.5 TgProRS exhibits varying sensitivity to HF when charging different types of tRNAPro 59 CHAPTER IV DISCUSSION 61 4.1 TgProRS exhibits relaxed substrate specificity 61 4.2 The motif 2 loop of TgProRS is essential for its dual recognition ability 62 4.3 TgProRS exhibits differential sensitivity to halofuginone when charging E- and P-type tRNAPro isoacceptors 63 CHAPTER V 65 CONCLUSIONS 65 CLOSING STATEMENTS 66 REFERENCES 67 APPENDIX A 71 APPENDIX B 75

    1. An S, Barany G, Musier-Forsyth K (2008) Evolution of acceptor stem tRNA recognition by class II prolyl-tRNA synthetase. Nucleic Acids Res 36: 2514-2521
    2. Arif A, Jia J, Mukhopadhyay R, Willard B, Kinter M, Fox PL (2009) Two-site phosphorylation of EPRS coordinates multimodal regulation of noncanonical translational control activity. Molecular cell 35: 164-180
    3. Banerjee B, Banerjee R (2014) Guanidine hydrochloride mediated denaturation of E. coli Alanyl-tRNA synthetase: identification of an inactive dimeric intermediate. Protein J 33: 119-127
    4. Banerjee B, Banerjee R (2015) Urea Unfolding Study of E. coli Alanyl-tRNA Synthetase and Its Monomeric Variants Proves the Role of C-Terminal Domain in Stability. J Amino Acids 2015: 805681
    5. Bartholow TG, Sanford BL, Cao B, Schmit HL, Johnson JM, Meitzner J, Bhattacharyya S, Musier-Forsyth K, Hati S (2014) Strictly conserved lysine of prolyl-tRNA Synthetase editing domain facilitates binding and positioning of misacylated tRNA(Pro.). Biochemistry 53: 1059-1068
    6. Betat H, Long Y, Jackman JE, Mörl M (2014) From end to end: tRNA editing at 5'- and 3'-terminal positions. Int J Mol Sci 15: 23975-23998
    7. Beuning PJ, Musier-Forsyth K (2001) Species-specific differences in amino acid editing by class II prolyl-tRNA synthetase. J Biol Chem 276: 30779-30785
    8. Burbaum JJ, Schimmel P (1991) Structural relationships and the classification of aminoacyl-tRNA synthetases. J Biol Chem 266: 16965-16968
    9. Burke B, Lipman RS, Shiba K, Musier-Forsyth K, Hou YM (2001) Divergent adaptation of tRNA recognition by Methanococcus jannaschii prolyl-tRNA synthetase. The Journal of biological chemistry 276: 20286-20291
    10. Burke B, Yang F, Chen F, Stehlin C, Chan B, Musier-Forsyth K (2000) Evolutionary coadaptation of the motif 2--acceptor stem interaction in the class II prolyl-tRNA synthetase system. Biochemistry 39: 15540-15547
    11. Carter CW, Jr. (1993) Cognition, mechanism, and evolutionary relationships in aminoacyl-tRNA synthetases. Annu Rev Biochem 62: 715-748
    12. Chaliotis A, Vlastaridis P, Mossialos D, Ibba M, Becker HD, Stathopoulos C, Amoutzias GD (2017) The complex evolutionary history of aminoacyl-tRNA synthetases. Nucleic acids research 45: 1059-1068
    13. Chang CP, Lin G, Chen SJ, Chiu WC, Chen WH, Wang CC (2008) Promoting the formation of an active synthetase/tRNA complex by a nonspecific tRNA-binding domain. J Biol Chem 283: 30699-30706
    14. Chang KJ, Lin G, Men LC, Wang CC (2006) Redundancy of non-AUG initiators. A clever mechanism to enhance the efficiency of translation in yeast. J Biol Chem 281: 7775-7783
    15. Chimnaronk S, Gravers Jeppesen M, Suzuki T, Nyborg J, Watanabe K (2005) Dual-mode recognition of noncanonical tRNAs(Ser) by seryl-tRNA synthetase in mammalian mitochondria. The EMBO journal 24: 3369-3379
    16. Chopra S, Palencia A, Virus C, Schulwitz S, Temple BR, Cusack S, Reader J (2016) Structural characterization of antibiotic self-immunity tRNA synthetase in plant tumour biocontrol agent. Nature communications 7: 12928
    17. Chopra S, Palencia A, Virus C, Tripathy A, Temple BR, Velazquez-Campoy A, Cusack S, Reader JS (2013) Plant tumour biocontrol agent employs a tRNA-dependent mechanism to inhibit leucyl-tRNA synthetase. Nature communications 4: 1417
    18. Cusack S, Yaremchuk A, Krikliviy I, Tukalo M (1998) tRNA(Pro) anticodon recognition by Thermus thermophilus prolyl-tRNA synthetase. Structure 6: 101-108
    19. Eriani G, Delarue M, Poch O, Gangloff J, Moras D (1990) Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature 347: 203-206
    20. Esseiva AC, Naguleswaran A, Hemphill A, Schneider A (2004) Mitochondrial tRNA import in Toxoplasma gondii. The Journal of biological chemistry 279: 42363-42368
    21. Fersht AR, Ashford JS, Bruton CJ, Jakes R, Koch GL, Hartley BS (1975) Active site titration and aminoacyl adenylate binding stoichiometry of aminoacyl-tRNA synthetases. Biochemistry 14: 1-4
    22. Gu W, Hurto RL, Hopper AK, Grayhack EJ, Phizicky EM (2005) Depletion of Saccharomyces cerevisiae tRNA(His) guanylyltransferase Thg1p leads to uncharged tRNAHis with additional m(5)C. Molecular and cellular biology 25: 8191-8201
    23. Hati S, Ziervogel B, Sternjohn J, Wong FC, Nagan MC, Rosen AE, Siliciano PG, Chihade JW, Musier-Forsyth K (2006) Pre-transfer editing by class II prolyl-tRNA synthetase: role of aminoacylation active site in "selective release" of noncognate amino acids. The Journal of biological chemistry 281: 27862-27872
    24. Hawko SA, Francklyn CS (2001) Covariation of a specificity-determining structural motif in an aminoacyl-tRNA synthetase and a tRNA identity element. Biochemistry 40: 1930-1936
    25. Heinemann IU, Nakamura A, O'Donoghue P, Eiler D, Söll D (2012) tRNAHis-guanylyltransferase establishes tRNAHis identity. Nucleic Acids Res 40: 333-344
    26. Horikoshi T, Noguchi H, Umehara T, Mutsuro-Aoki H, Kurihara R, Noguchi R, Hashimoto T, Watanabe Y, Ando T, Kamata K et al (2021) Crystal structure of Nanoarchaeum equitans tyrosyl-tRNA synthetase and its aminoacylation activity toward tRNA(Tyr) with an extra guanosine residue at the 5'-terminus. Biochem Biophys Res Commun 575: 90-95
    27. Howard MJ, Liu X, Lim WH, Klemm BP, Fierke CA, Koutmos M, Engelke DR (2013) RNase P enzymes: divergent scaffolds for a conserved biological reaction. RNA Biol 10: 909-914
    28. Hyouta Himeno TH, Takuya Ueda, Kimitsuna Watanabe, Kin-ichiro Miura, and Mikio Shimizu (1989) Role of the extra G-C pair at the end of the acceptor stem of tRNAHIs in aminoacylation. Nucleic Acid Research 17: 9
    29. Ibba M, Soll D (2000) Aminoacyl-tRNA synthesis. Annu Rev Biochem 69: 617-650
    30. Ivanesthi IR, Latifah E, Amrullah LF, Tseng YK, Chuang TH, Pan HC, Yang CS, Liu SY, Wang CC (2024) Adaptation of a eukaryote-like ProRS to a prokaryote-like tRNAPro. Nucleic acids research 52: 7158-7170
    31. Ivanesthi IR, Latifah E, Liu SY, Tseng YK, Pan HC, Wang CC (2025) Dual-mode recognition of tRNA(Pro) isoacceptors by Toxoplasma gondii Prolyl-tRNA synthetase. EMBO reports 26: 2931-2944
    32. Jain V, Kikuchi H, Oshima Y, Sharma A, Yogavel M (2014) Structural and functional analysis of the anti-malarial drug target prolyl-tRNA synthetase. Journal of structural and functional genomics 15: 181-190
    33. Jain V, Yogavel M, Kikuchi H, Oshima Y, Hariguchi N, Matsumoto M, Goel P, Touquet B, Jumani RS, Tacchini-Cottier F et al (2017) Targeting Prolyl-tRNA Synthetase to Accelerate Drug Discovery against Malaria, Leishmaniasis, Toxoplasmosis, Cryptosporidiosis, and Coccidiosis. Structure (London, England : 1993) 25: 1495-1505.e1496
    34. Jain V, Yogavel M, Oshima Y, Kikuchi H, Touquet B, Hakimi MA, Sharma A (2015) Structure of Prolyl-tRNA Synthetase-Halofuginone Complex Provides Basis for Development of Drugs against Malaria and Toxoplasmosis. Structure 23: 819-829
    35. Katsyv I, Wang M, Song WM, Zhou X, Zhao Y, Park S, Zhu J, Zhang B, Irie HY (2016) EPRS is a critical regulator of cell proliferation and estrogen signaling in ER + breast cancer. 7
    36. Kim MH, Kang BS (2022) Structure and Dynamics of the Human Multi-tRNA Synthetase Complex. Sub-cellular biochemistry 99: 199-233
    37. Kwon NH, Fox PL, Kim S (2019) Aminoacyl-tRNA synthetases as therapeutic targets. Nat Rev Drug Discov 18: 629-650
    38. Latifah E, Ivanesthi IR, Tseng Y-K, Pan H-C, Wang C-C (2024) Adaptive evolution: Eukaryotic enzyme's specificity shift to a bacterial substrate. 33: e5028
    39. Lee J, Joshi N, Pasini R, Dobson RC, Allison J, Leustek T (2016) Inhibition of Arabidopsis growth by the allelopathic compound azetidine-2-carboxylate is due to the low amino acid specificity of cytosolic prolyl-tRNA synthetase. The Plant journal : for cell and molecular biology 88: 236-246
    40. Lee YH, Chang CP, Cheng YJ, Kuo YY, Lin YS, Wang CC (2017) Evolutionary gain of highly divergent tRNA specificities by two isoforms of human histidyl-tRNA synthetase. Cell Mol Life Sci 74: 2663-2677
    41. Lee YH, Lo YT, Chang CP, Yeh CS, Chang TH, Chen YW, Tseng YK, Wang CC (2019) Naturally occurring dual recognition of tRNA(His) substrates with and without a universal identity element. RNA Biol 16: 1275-1285
    42. Liu H, Peterson R, Kessler J, Musier-Forsyth K (1995) Molecular recognition of tRNA(Pro) by Escherichia coli proline tRNA synthetase in vitro. Nucleic Acids Res 23: 165-169
    43. Lorenz C, Lünse CE, Mörl M (2017) tRNA Modifications: Impact on Structure and Thermal Adaptation. Biomolecules 7
    44. Manickam Y, Malhotra N, Mishra S, Babbar P, Dusane A, Laleu B, Bellini V, Hakimi MA, Bougdour A, Sharma A (2022) Double drugging of prolyl-tRNA synthetase provides a new paradigm for anti-infective drug development. PLoS pathogens 18: e1010363
    45. Michel Fromant PP, and Sylvain Blanquet (2000) Function of the Extra 5′-Phosphate Carried by Histidine tRNA. Biochemistry 39: 6
    46. Musier-Forsyth AERaK (2004) Recognition of G-1:C73 Atomic Groups by Escherichia coli Histidyl-tRNA Synthetase. Biochemistry 126: 2
    47. Nameki N, Tadaki T, Muto A, Himeno H (1999) Amino acid acceptor identity switch of Escherichia coli tmRNA from alanine to histidine in vitro. Journal of molecular biology 289: 1-7
    48. Nasim F, Qureshi IA (2023) Aminoacyl tRNA Synthetases: Implications of Structural Biology in Drug Development against Trypanosomatid Parasites. ACS omega 8: 14884-14899
    49. Natsoulis G, Hilger F, Fink GR (1986) The HTS1 gene encodes both the cytoplasmic and mitochondrial histidine tRNA synthetases of S. cerevisiae. Cell 46: 235-243
    50. Nobukazu Nameki HA, Mikio Shimizu, Norihiro Okada and Hyouta Himeno (1995) Identity elements of Saccharomyces cerevisiae tRNA™8. Nucleic Acids Research 23: 6
    51. Oslowski CM, Urano F (2011) Measuring ER stress and the unfolded protein response using mammalian tissue culture system. Methods Enzymol 490: 71-92
    52. Pena N, Dranow DM, Hu Y, Escamilla Y, Bullard JM (2019) Characterization and structure determination of prolyl-tRNA synthetase from Pseudomonas aeruginosa and development as a screening platform. Protein Sci 28: 727-737
    53. Pino P, Aeby E, Foth BJ, Sheiner L, Soldati T, Schneider A, Soldati-Favre D (2010) Mitochondrial translation in absence of local tRNA aminoacylation and methionyl tRNA Met formylation in Apicomplexa. Molecular microbiology 76: 706-718
    54. Randau L, Schröder I, Söll D (2008) Life without RNase P. Nature 453: 120-123
    55. Rubio M, Napolitano M, Ochoa de Alda JA, Santamaría-Gómez J, Patterson CJ, Foster AW, Bru-Martínez R, Robinson NJ, Luque I (2015) Trans-oligomerization of duplicated aminoacyl-tRNA synthetases maintains genetic code fidelity under stress. Nucleic acids research 43: 9905-9917
    56. Sanahuja G, Banakar R, Twyman RM, Capell T, Christou P (2011) Bacillus thuringiensis: a century of research, development and commercial applications. Plant Biotechnol J 9: 283-300
    57. Shiba K, Stello T, Motegi H, Noda T, Musier-Forsyth K, Schimmel P (1997) Human lysyl-tRNA synthetase accepts nucleotide 73 variants and rescues Escherichia coli double-defective mutant. The Journal of biological chemistry 272: 22809-22816
    58. Shimada N, Suzuki T, Watanabe K (2001) Dual mode recognition of two isoacceptor tRNAs by mammalian mitochondrial seryl-tRNA synthetase. The Journal of biological chemistry 276: 46770-46778
    59. Song Y, Zhou H, Vo MN, Shi Y, Nawaz MH, Vargas-Rodriguez O, Diedrich JK, Yates JR, Kishi S, Musier-Forsyth K et al (2017) Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid. Nature communications 8: 2281
    60. Stehlin C, Burke B, Yang F, Liu H, Shiba K, Musier-Forsyth K (1998) Species-specific differences in the operational RNA code for aminoacylation of tRNAPro. Biochemistry 37: 8605-8613
    61. Steiner RE, Kyle AM, Ibba M (2019) Oxidation of phenylalanyl-tRNA synthetase positively regulates translational quality control. Proc Natl Acad Sci U S A 116: 10058-10063
    62. SternJohn J, Hati S, Siliciano PG, Musier-Forsyth K (2007) Restoring species-specific posttransfer editing activity to a synthetase with a defunct editing domain. Proceedings of the National Academy of Sciences of the United States of America 104: 2127-2132
    63. Susan A. Connolly AER, Karin Musier-Forsyth, and Christopher S. Francklyn (2004) G-1:C73 Recognition by an Arginine Cluster in the Active Site of Escherichia coli Histidyl-tRNA Synthetase. Biochemistry 43: 8
    64. Tang HL, Yeh LS, Chen NK, Ripmaster T, Schimmel P, Wang CC (2004) Translation of a yeast mitochondrial tRNA synthetase initiated at redundant non-AUG codons. J Biol Chem 279: 49656-49663
    65. Tian Q, Wang C, Liu Y, Xie W (2015) Structural basis for recognition of G-1-containing tRNA by histidyl-tRNA synthetase. Nucleic Acids Res 43: 2980-2990
    66. Tye MA, Payne NC, Johansson C, Singh K, Santos SA, Fagbami L, Pant A, Sylvester K, Luth MR, Marques S et al (2022) Elucidating the path to Plasmodium prolyl-tRNA synthetase inhibitors that overcome halofuginone resistance. Nat Commun 13: 4976
    67. Vargas-Rodriguez O, Musier-Forsyth K (2013) Exclusive use of trans-editing domains prevents proline mistranslation. The Journal of biological chemistry 288: 14391-14399
    68. Wen Yan JA, and Christopher Francklyn (1996) A tRNA Identity Switch Mediated by the Binding Interaction between a tRNA Anticodon and the Accessory Domain of a Class II Aminoacyl-tRNA Synthetas. Biochemistry 35: 10
    69. Yaremchuk A, Cusack S, Tukalo M (2000) Crystal structure of a eukaryote/archaeon-like protyl-tRNA synthetase and its complex with tRNAPro(CGG). The EMBO journal 19: 4745-4758
    70. Yogavel M, Bougdour A, Mishra S, Malhotra N, Chhibber-Goel J, Bellini V, Harlos K, Laleu B, Hakimi MA, Sharma A (2023) Targeting prolyl-tRNA synthetase via a series of ATP-mimetics to accelerate drug discovery against toxoplasmosis. PLoS pathogens 19: e1011124
    71. Zanki V, Bozic B, Mocibob M, Ban N, Gruic-Sovulj I (2022) A pair of isoleucyl-tRNA synthetases in Bacilli fulfills complementary roles to keep fast translation and provide antibiotic resistance. Protein Sci 31: e4418

    QR CODE
    :::