4eg3 › Citations

Distinct states of methionyl-tRNA synthetase indicate inhibitor binding by conformational selection.

Koh CY, Kim JE, Shibata S, Ranade RM, Yu M, Liu J, Gillespie JR, Buckner FS, Verlinde CL, Fan E, Hol WG
Structure 20 1681-91 (2012)
Related entries: 4eg1, 4eg4, 4eg5, 4eg6, 4eg7, 4eg8, 4ega

Cited: 47 times
EuropePMC logo PMID: 22902861

Abstract

To guide development of new drugs targeting methionyl-tRNA synthetase (MetRS) for treatment of human African trypanosomiasis, crystal structure determinations of Trypanosoma brucei MetRS in complex with its substrate methionine and its intermediate product methionyl-adenylate were followed by those of the enzyme in complex with high-affinity aminoquinolone inhibitors via soaking experiments. Drastic changes in conformation of one of the two enzymes in the asymmetric unit allowed these inhibitors to occupy an enlarged methionine pocket and a new so-called auxiliary pocket. Interestingly, a small low-affinity compound caused the same conformational changes, removed the methionine without occupying the methionine pocket, and occupied the previously not existing auxiliary pocket. Analysis of these structures indicates that the binding of the inhibitors is the result of conformational selection, not induced fit.

Reviews - 4eg3 mentioned but not cited (1)

  1. The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations. Ogungbe IV, Setzer WN. Molecules 21 (2016)

Articles - 4eg3 mentioned but not cited (5)

  1. Distinct states of methionyl-tRNA synthetase indicate inhibitor binding by conformational selection. Koh CY, Kim JE, Shibata S, Ranade RM, Yu M, Liu J, Gillespie JR, Buckner FS, Verlinde CL, Fan E, Hol WG. Structure 20 1681-1691 (2012)
  2. Structures of Trypanosoma brucei methionyl-tRNA synthetase with urea-based inhibitors provide guidance for drug design against sleeping sickness. Koh CY, Kim JE, Wetzel AB, de van der Schueren WJ, Shibata S, Ranade RM, Liu J, Zhang Z, Gillespie JR, Buckner FS, Verlinde CL, Fan E, Hol WG. PLoS Negl Trop Dis 8 e2775 (2014)
  3. Chemical Validation of Methionyl-tRNA Synthetase as a Druggable Target in Leishmania donovani. Torrie LS, Brand S, Robinson DA, Ko EJ, Stojanovski L, Simeons FRC, Wyllie S, Thomas J, Ellis L, Osuna-Cabello M, Epemolu O, Nühs A, Riley J, MacLean L, Manthri S, Read KD, Gilbert IH, Fairlamb AH, De Rycker M. ACS Infect Dis 3 718-727 (2017)
  4. Structural characterization of free-state and product-state Mycobacterium tuberculosis methionyl-tRNA synthetase reveals an induced-fit ligand-recognition mechanism. Wang W, Qin B, Wojdyla JA, Wang M, Gao X, Cui S. IUCrJ 5 478-490 (2018)
  5. The crystal structure of the drug target Mycobacterium tuberculosis methionyl-tRNA synthetase in complex with a catalytic intermediate. Barros-Álvarez X, Turley S, Ranade RM, Gillespie JR, Duster NA, Verlinde CLMJ, Fan E, Buckner FS, Hol WGJ. Acta Crystallogr F Struct Biol Commun 74 245-254 (2018)


Reviews citing this publication (12)

  1. Aminoacyl-tRNA synthetases as drug targets in eukaryotic parasites. Pham JS, Dawson KL, Jackson KE, Lim EE, Pasaje CF, Turner KE, Ralph SA. Int J Parasitol Drugs Drug Resist 4 1-13 (2014)
  2. Multiple conformational selection and induced fit events take place in allosteric propagation. Nussinov R, Ma B, Tsai CJ. Biophys. Chem. 186 22-30 (2014)
  3. Single molecule insights on conformational selection and induced fit mechanism. Hatzakis NS. Biophys. Chem. 186 46-54 (2014)
  4. Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification. Fang P, Guo M. Life (Basel) 5 1703-1725 (2015)
  5. Protein Flexibility in Drug Discovery: From Theory to Computation. Buonfiglio R, Recanatini M, Masetti M. ChemMedChem 10 1141-1148 (2015)
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  7. Aminoacyl-tRNA Synthetases as Valuable Targets for Antimicrobial Drug Discovery. Pang L, Weeks SD, Van Aerschot A. Int J Mol Sci 22 1750 (2021)
  8. Rate Constants and Mechanisms of Protein-Ligand Binding. Pang X, Zhou HX. Annu Rev Biophys 46 105-130 (2017)
  9. Polyamine-based analogs and conjugates as antikinetoplastid agents. Jagu E, Pomel S, Pethe S, Loiseau PM, Labruère R. Eur J Med Chem 139 982-1015 (2017)
  10. Three-dimensional structures in the design of therapeutics targeting parasitic protozoa: reflections on the past, present and future. Hol WG. Acta Crystallogr F Struct Biol Commun 71 485-499 (2015)
  11. Aminoacyl tRNA Synthetases: Implications of Structural Biology in Drug Development against Trypanosomatid Parasites. Nasim F, Qureshi IA. ACS Omega 8 14884-14899 (2023)
  12. Pharmacological Potential and Synthetic Approaches of Imidazo[4,5-b]pyridine and Imidazo[4,5-c]pyridine Derivatives. Krause M, Foks H, Gobis K. Molecules 22 (2017)

Articles citing this publication (29)

  1. Structure of Prolyl-tRNA Synthetase-Halofuginone Complex Provides Basis for Development of Drugs against Malaria and Toxoplasmosis. Jain V, Yogavel M, Oshima Y, Kikuchi H, Touquet B, Hakimi MA, Sharma A. Structure 23 819-829 (2015)
  2. Identification of potent inhibitors of the Trypanosoma brucei methionyl-tRNA synthetase via high-throughput orthogonal screening. Pedró-Rosa L, Buckner FS, Ranade RM, Eberhart C, Madoux F, Gillespie JR, Koh CY, Brown S, Lohse J, Verlinde CL, Fan E, Bannister T, Scampavia L, Hol WG, Spicer T, Hodder P. J Biomol Screen 20 122-130 (2015)
  3. A multiple aminoacyl-tRNA synthetase complex that enhances tRNA-aminoacylation in African trypanosomes. Cestari I, Kalidas S, Monnerat S, Anupama A, Phillips MA, Stuart K. Mol. Cell. Biol. 33 4872-4888 (2013)
  4. Crystal structures of Plasmodium falciparum cytosolic tryptophanyl-tRNA synthetase and its potential as a target for structure-guided drug design. Koh CY, Kim JE, Napoli AJ, Verlinde CL, Fan E, Buckner FS, Van Voorhis WC, Hol WG. Mol. Biochem. Parasitol. 189 26-32 (2013)
  5. Genetic validation of aminoacyl-tRNA synthetases as drug targets in Trypanosoma brucei. Kalidas S, Cestari I, Monnerat S, Li Q, Regmi S, Hasle N, Labaied M, Parsons M, Stuart K, Phillips MA. Eukaryotic Cell 13 504-516 (2014)
  6. Induced resistance to methionyl-tRNA synthetase inhibitors in Trypanosoma brucei is due to overexpression of the target. Ranade RM, Gillespie JR, Shibata S, Verlinde CL, Fan E, Hol WG, Buckner FS. Antimicrob. Agents Chemother. 57 3021-3028 (2013)
  7. Inhibition of protein synthesis and malaria parasite development by drug targeting of methionyl-tRNA synthetases. Hussain T, Yogavel M, Sharma A. Antimicrob. Agents Chemother. 59 1856-1867 (2015)
  8. Inhibitors of methionyl-tRNA synthetase have potent activity against Giardia intestinalis trophozoites. Ranade RM, Zhang Z, Gillespie JR, Shibata S, Verlinde CL, Hol WG, Fan E, Buckner FS. Antimicrob. Agents Chemother. 59 7128-7131 (2015)
  9. Conformational heterogeneity in apo and drug-bound structures of Toxoplasma gondii prolyl-tRNA synthetase. Mishra S, Malhotra N, Kumari S, Sato M, Kikuchi H, Yogavel M, Sharma A. Acta Crystallogr F Struct Biol Commun 75 714-724 (2019)
  10. Inhibition of isoleucyl-tRNA synthetase as a potential treatment for human African Trypanosomiasis. Cestari I, Stuart K. J. Biol. Chem. 288 14256-14263 (2013)
  11. 5-Fluoroimidazo[4,5-b]pyridine Is a Privileged Fragment That Conveys Bioavailability to Potent Trypanosomal Methionyl-tRNA Synthetase Inhibitors. Zhang Z, Koh CY, Ranade RM, Shibata S, Gillespie JR, Hulverson MA, Huang W, Nguyen J, Pendem N, Gelb MH, Verlinde CL, Hol WG, Buckner FS, Fan E. ACS Infect Dis 2 399-404 (2016)
  12. Design, Synthesis, and Evaluation of Novel Anti-Trypanosomal Compounds. Lepovitz LT, Meis AR, Thomas SM, Wiedeman J, Pham A, Mensa-Wilmot K, Martin SF. Tetrahedron 76 131086 (2020)
  13. Structure-guided design of novel Trypanosoma brucei Methionyl-tRNA synthetase inhibitors. Huang W, Zhang Z, Barros-Álvarez X, Koh CY, Ranade RM, Gillespie JR, Creason SA, Shibata S, Verlinde CLMJ, Hol WGJ, Buckner FS, Fan E. Eur J Med Chem 124 1081-1092 (2016)
  14. From Cells to Mice to Target: Characterization of NEU-1053 (SB-443342) and Its Analogues for Treatment of Human African Trypanosomiasis. Devine WG, Diaz-Gonzalez R, Ceballos-Perez G, Rojas D, Satoh T, Tear W, Ranade RM, Barros-Álvarez X, Hol WG, Buckner FS, Navarro M, Pollastri MP. ACS Infect Dis 3 225-236 (2017)
  15. Spontaneous Selection of Cryptosporidium Drug Resistance in a Calf Model of Infection. Hasan MM, Stebbins EE, Choy RKM, Gillespie JR, de Hostos EL, Miller P, Mushtaq A, Ranade RM, Teixeira JE, Verlinde CLMJ, Sateriale A, Zhang Z, Osbourn DM, Griggs DW, Fan E, Buckner FS, Huston CD. Antimicrob Agents Chemother 65 e00023-21 (2021)
  16. Molecular basis for diaryldiamine selectivity and competition with tRNA in a type 2 methionyl-tRNA synthetase from a Gram-negative bacterium. Mercaldi GF, Andrade MO, Zanella JL, Cordeiro AT, Benedetti CE. J Biol Chem 296 100658 (2021)
  17. Novel hybrid virtual screening protocol based on molecular docking and structure-based pharmacophore for discovery of methionyl-tRNA synthetase inhibitors as antibacterial agents. Liu C, He G, Jiang Q, Han B, Peng C. Int J Mol Sci 14 14225-14239 (2013)
  18. Structural basis for the dynamics of human methionyl-tRNA synthetase in multi-tRNA synthetase complexes. Kim DK, Lee HJ, Kong J, Cho HY, Kim S, Kang BS. Nucleic Acids Res 49 6549-6568 (2021)
  19. Comparison of histidine recognition in human and trypanosomatid histidyl-tRNA synthetases. Koh CY, Wetzel AB, de van der Schueren WJ, Hol WG. Biochimie 106 111-120 (2014)
  20. Ligand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms. Moen SO, Edwards TE, Dranow DM, Clifton MC, Sankaran B, Van Voorhis WC, Sharma A, Manoil C, Staker BL, Myler PJ, Lorimer DD. Sci Rep 7 223 (2017)
  21. Aminoacyl tRNA synthetases as malarial drug targets: a comparative bioinformatics study. Nyamai DW, Tastan Bishop Ö. Malar. J. 18 34 (2019)
  22. Discovery of an Allosteric Binding Site in Kinetoplastid Methionyl-tRNA Synthetase. Torrie LS, Robinson DA, Thomas MG, Hobrath JV, Shepherd SM, Post JM, Ko EJ, Ferreira RA, Mackenzie CJ, Wrobel K, Edwards DP, Gilbert IH, Gray DW, Fairlamb AH, De Rycker M. ACS Infect Dis 6 1044-1057 (2020)
  23. Double drugging of prolyl-tRNA synthetase provides a new paradigm for anti-infective drug development. Manickam Y, Malhotra N, Mishra S, Babbar P, Dusane A, Laleu B, Bellini V, Hakimi MA, Bougdour A, Sharma A. PLoS Pathog 18 e1010363 (2022)
  24. Exploring Proteus mirabilis Methionine tRNA Synthetase Active Site: Homology Model Construction, Molecular Dynamics, Pharmacophore and Docking Validation. Elbaramawi SS, Eissa AG, Noureldin NA, Simons C. Pharmaceuticals (Basel) 16 1263 (2023)
  25. Fragment screening and structural analyses highlight the ATP-assisted ligand binding for inhibitor discovery against type 1 methionyl-tRNA synthetase. Yi J, Cai Z, Qiu H, Lu F, Luo Z, Chen B, Gu Q, Xu J, Zhou H. Nucleic Acids Res gkac285 (2022)
  26. Optimization of Methionyl tRNA-Synthetase Inhibitors for Treatment of Cryptosporidium Infection. Buckner FS, Ranade RM, Gillespie JR, Shibata S, Hulverson MA, Zhang Z, Huang W, Choi R, Verlinde CLMJ, Hol WGJ, Ochida A, Akao Y, Choy RKM, Van Voorhis WC, Arnold SLM, Jumani RS, Huston CD, Fan E. Antimicrob. Agents Chemother. 63 (2019)
  27. Optimization of a binding fragment targeting the "enlarged methionine pocket" leads to potent Trypanosoma brucei methionyl-tRNA synthetase inhibitors. Huang W, Zhang Z, Ranade RM, Gillespie JR, Barros-Álvarez X, Creason SA, Shibata S, Verlinde CLMJ, Hol WGJ, Buckner FS, Fan E. Bioorg. Med. Chem. Lett. 27 2702-2707 (2017)
  28. Structure-guided discovery of selective methionyl-tRNA synthetase inhibitors with potent activity against Trypanosoma brucei. Zhang Z, Barros-Álvarez X, Gillespie JR, Ranade RM, Huang W, Shibata S, Molasky NMR, Faghih O, Mushtaq A, Choy RKM, de Hostos E, Hol WGJ, Verlinde CLMJ, Buckner FS, Fan E. RSC Med Chem 11 885-895 (2020)
  29. Targeting prolyl-tRNA synthetase via a series of ATP-mimetics to accelerate drug discovery against toxoplasmosis. Yogavel M, Bougdour A, Mishra S, Malhotra N, Chhibber-Goel J, Bellini V, Harlos K, Laleu B, Hakimi MA, Sharma A. PLoS Pathog 19 e1011124 (2023)


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