6az1 › Citations

Atomic resolution snapshot of Leishmania ribosome inhibition by the aminoglycoside paromomycin.

Fig. 1
Fig. 2
Fig. 3
Shalev-Benami M, Zhang Y, Rozenberg H, Nobe Y, Taoka M, Matzov D, Zimmerman E, Bashan A, Isobe T, Jaffe CL, Yonath A, Skiniotis G
OpenAccess logo Nat Commun 8 1589 (2017)
Cited: 42 times
EuropePMC logo PMID: 29150609

Abstract

Leishmania is a single-celled eukaryotic parasite afflicting millions of humans worldwide, with current therapies limited to a poor selection of drugs that mostly target elements in the parasite's cell envelope. Here we determined the atomic resolution electron cryo-microscopy (cryo-EM) structure of the Leishmania ribosome in complex with paromomycin (PAR), a highly potent compound recently approved for treatment of the fatal visceral leishmaniasis (VL). The structure reveals the mechanism by which the drug induces its deleterious effects on the parasite. We further show that PAR interferes with several aspects of cytosolic translation, thus highlighting the cytosolic rather than the mitochondrial ribosome as the primary drug target. The results also highlight unique as well as conserved elements in the PAR-binding pocket that can serve as hotspots for the development of novel therapeutics.

Articles - 6az1 mentioned but not cited (8)

  1. Measurement of atom resolvability in cryo-EM maps with Q-scores. Pintilie G, Zhang K, Su Z, Li S, Schmid MF, Chiu W. Nat Methods 17 328-334 (2020)
  2. Atomic resolution snapshot of Leishmania ribosome inhibition by the aminoglycoside paromomycin. Shalev-Benami M, Zhang Y, Rozenberg H, Nobe Y, Taoka M, Matzov D, Zimmerman E, Bashan A, Isobe T, Jaffe CL, Yonath A, Skiniotis G. Nat Commun 8 1589 (2017)
  3. GemSpot: A Pipeline for Robust Modeling of Ligands into Cryo-EM Maps. Robertson MJ, van Zundert GCP, Borrelli K, Skiniotis G. Structure 28 707-716.e3 (2020)
  4. Probing small ribosomal subunit RNA helix 45 acetylation across eukaryotic evolution. Bortolin-Cavaillé ML, Quillien A, Thalalla Gamage S, Thomas JM, Sas-Chen A, Sharma S, Plisson-Chastang C, Vandel L, Blader P, Lafontaine DLJ, Schwartz S, Meier JL, Cavaillé J. Nucleic Acids Res 50 6284-6299 (2022)
  5. Base-intercalated and base-wedged stacking elements in 3D-structure of RNA and RNA-protein complexes. Baulin E, Metelev V, Bogdanov A. Nucleic Acids Res 48 8675-8685 (2020)
  6. A single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei. Rajan KS, Madmoni H, Bashan A, Taoka M, Aryal S, Nobe Y, Doniger T, Galili Kostin B, Blumberg A, Cohen-Chalamish S, Schwartz S, Rivalta A, Zimmerman E, Unger R, Isobe T, Yonath A, Michaeli S. Nat Commun 14 7462 (2023)
  7. Cryo-EM structure of the highly atypical cytoplasmic ribosome of Euglena gracilis. Matzov D, Taoka M, Nobe Y, Yamauchi Y, Halfon Y, Asis N, Zimermann E, Rozenberg H, Bashan A, Bhushan S, Isobe T, Gray MW, Yonath A, Shalev-Benami M. Nucleic Acids Res 48 11750-11761 (2020)
  8. Unusual tertiary pairs in eukaryotic tRNAAla. Westhof E, Liang S, Tong X, Ding X, Zheng L, Dai F. RNA 26 1519-1529 (2020)


Reviews citing this publication (9)

  1. Cryo-EM in drug discovery: achievements, limitations and prospects. Renaud JP, Chari A, Ciferri C, Liu WT, Rémigy HW, Stark H, Wiesmann C. Nat Rev Drug Discov 17 471-492 (2018)
  2. Drug discovery in the era of cryo-electron microscopy. Robertson MJ, Meyerowitz JG, Skiniotis G. Trends Biochem Sci 47 124-135 (2022)
  3. Targeting the Human 80S Ribosome in Cancer: From Structure to Function and Drug Design for Innovative Adjuvant Therapeutic Strategies. Gilles A, Frechin L, Natchiar K, Biondani G, Loeffelholz OV, Holvec S, Malaval JL, Winum JY, Klaholz BP, Peyron JF. Cells 9 (2020)
  4. Cryo-EM for Small Molecules Discovery, Design, Understanding, and Application. Scapin G, Potter CS, Carragher B. Cell Chem Biol 25 1318-1325 (2018)
  5. Anti-trypanosomatid drug discovery: progress and challenges. De Rycker M, Wyllie S, Horn D, Read KD, Gilbert IH. Nat Rev Microbiol 21 35-50 (2023)
  6. Can We Harness Immune Responses to Improve Drug Treatment in Leishmaniasis? Aruleba RT, Carter KC, Brombacher F, Hurdayal R. Microorganisms 8 (2020)
  7. Exploring the Structural Variability of Dynamic Biological Complexes by Single-Particle Cryo-Electron Microscopy. DiIorio MC, Kulczyk AW. Micromachines (Basel) 14 118 (2022)
  8. Graph Theoretical Methods and Workflows for Searching and Annotation of RNA Tertiary Base Motifs and Substructures. Emrizal R, Hamdani HY, Firdaus-Raih M. Int J Mol Sci 22 8553 (2021)
  9. Interaction Networks of Ribosomal Expansion Segments in Kinetoplastids. Vicens Q, Bochler A, Jobe A, Frank J, Hashem Y. Subcell Biochem 96 433-450 (2021)

Articles citing this publication (25)

  1. Reprofiling of approved drugs against SARS-CoV-2 main protease: an in-silico study. Kumar P, Bhardwaj T, Kumar A, Gehi BR, Kapuganti SK, Garg N, Nath G, Giri R. J Biomol Struct Dyn 40 3170-3184 (2022)
  2. Landscape of the complete RNA chemical modifications in the human 80S ribosome. Taoka M, Nobe Y, Yamaki Y, Sato K, Ishikawa H, Izumikawa K, Yamauchi Y, Hirota K, Nakayama H, Takahashi N, Isobe T. Nucleic Acids Res. 46 9289-9298 (2018)
  3. The large repertoire of 2'-O-methylation guided by C/D snoRNAs on Trypanosoma brucei rRNA. Rajan KS, Zhu Y, Adler K, Doniger T, Cohen-Chalamish S, Srivastava A, Shalev-Benami M, Matzov D, Unger R, Tschudi C, Günzl A, Carmichael GG, Michaeli S. RNA Biol 17 1018-1039 (2020)
  4. A fully automatic method yielding initial models from high-resolution cryo-electron microscopy maps. Terwilliger TC, Adams PD, Afonine PV, Sobolev OV. Nat. Methods 15 905-908 (2018)
  5. Genome instability drives epistatic adaptation in the human pathogen Leishmania. Bussotti G, Piel L, Pescher P, Domagalska MA, Rajan KS, Cohen-Chalamish S, Doniger T, Hiregange DG, Myler PJ, Unger R, Michaeli S, Späth GF. Proc Natl Acad Sci U S A 118 e2113744118 (2021)
  6. Structural basis for LeishIF4E-1 modulation by an interacting protein in the human parasite Leishmania major. Meleppattu S, Arthanari H, Zinoviev A, Boeszoermenyi A, Wagner G, Shapira M, Léger-Abraham M. Nucleic Acids Res. 46 3791-3801 (2018)
  7. Factors influencing readthrough therapy for frequent cystic fibrosis premature termination codons. Pranke I, Bidou L, Martin N, Blanchet S, Hatton A, Karri S, Cornu D, Costes B, Chevalier B, Tondelier D, Girodon E, Coupet M, Edelman A, Fanen P, Namy O, Sermet-Gaudelus I, Hinzpeter A. ERJ Open Res 4 (2018)
  8. Quantitative Proteomics Reveals that Hsp90 Inhibition Dynamically Regulates Global Protein Synthesis in Leishmania mexicana. Kalesh K, Sundriyal S, Perera H, Cobb SL, Denny PW. mSystems 6 e00089-21 (2021)
  9. Small nucleolar RNAs controlling rRNA processing in Trypanosoma brucei. Chikne V, Shanmugha Rajan K, Shalev-Benami M, Decker K, Cohen-Chalamish S, Madmoni H, Biswas VK, Kumar Gupta S, Doniger T, Unger R, Tschudi C, Ullu E, Michaeli S. Nucleic Acids Res. 47 2609-2629 (2019)
  10. A unified approach to sequential and non-sequential structure alignment of proteins, RNAs, and DNAs. Zhang C, Pyle AM. iScience 25 105218 (2022)
  11. Oral Delivery of miR-320-3p with Lipidic Aminoglycoside Derivatives at Mid-Lactation Alters miR-320-3p Endogenous Levels in the Gut and Brain of Adult Rats According to Early or Regular Weaning. Tavares GA, Torres A, Le Drean G, Queignec M, Castellano B, Tesson L, Remy S, Anegon I, Pitard B, Kaeffer B. Int J Mol Sci 24 191 (2022)
  12. A Pattern Recognition Tool for Medium-resolution Cryo-EM Density Maps and Low-resolution Cryo-ET Density maps. Haslam D, Sazzed S, Wriggers W, Kovcas J, Song J, Auer M, He J. Bioinform Res Appl (2018) 10847 233-238 (2018)
  13. A dual role of the ribosome-bound chaperones RAC/Ssb in maintaining the fidelity of translation termination. Gribling-Burrer AS, Chiabudini M, Zhang Y, Qiu Z, Scazzari M, Wölfle T, Wohlwend D, Rospert S. Nucleic Acids Res. 47 7018-7034 (2019)
  14. Activity of paromomycin against Leishmania amazonensis: Direct correlation between susceptibility in vitro and the treatment outcome in vivo. Coser EM, Ferreira BA, Branco N, Yamashiro-Kanashiro EH, Lindoso JAL, Coelho AC. Int J Parasitol Drugs Drug Resist 14 91-98 (2020)
  15. An Investigation of Atomic Structures Derived from X-ray Crystallography and Cryo-Electron Microscopy Using Distal Blocks of Side-Chains. Chen L, He J, Sazzed S, Walker R. Molecules 23 (2018)
  16. Comparative analysis of the transcriptional responses of five Leishmania species to trivalent antimony. Medina J, Cruz-Saavedra L, Patiño LH, Muñoz M, Ramírez JD. Parasit Vectors 14 419 (2021)
  17. Conjugation of Gentamicin to Polyamidoamine Dendrimers Improved Anti-bacterial Properties against Pseudomonas aeruginosa. Sheykhloo H, Milani M, Najafi F, Bani F, Zarebkohan A. Adv Pharm Bull 11 675-683 (2021)
  18. Coupling chemical mutagenesis to next generation sequencing for the identification of drug resistance mutations in Leishmania. Bhattacharya A, Leprohon P, Bigot S, Padmanabhan PK, Mukherjee A, Roy G, Gingras H, Mestdagh A, Papadopoulou B, Ouellette M. Nat Commun 10 5627 (2019)
  19. Cryo-EM structure of the ancient eukaryotic ribosome from the human parasite Giardia lamblia. Hiregange DG, Rivalta A, Bose T, Breiner-Goldstein E, Samiya S, Cimicata G, Kulakova L, Zimmerman E, Bashan A, Herzberg O, Yonath A. Nucleic Acids Res 50 1770-1782 (2022)
  20. Eukaryotic tRNA sequences present conserved and amino acid-specific structural signatures. Westhof E, Thornlow B, Chan PP, Lowe TM. Nucleic Acids Res 50 4100-4112 (2022)
  21. Isolation, typing, and drug susceptibility of Leishmania (Leishmania) infantum isolates from dogs of the municipality of Embu das Artes, an endemic region for canine leishmaniasis in Brazil. Ferreira BA, Martins TFC, Coser EM, da L Oliveira V, Yamashiro-Kanashiro EH, Rocha MC, Pinto MM, Cotrim PC, Coelho AC. Parasitol Res 121 2683-2695 (2022)
  22. METTL15 introduces N4-methylcytidine into human mitochondrial 12S rRNA and is required for mitoribosome biogenesis. Van Haute L, Hendrick AG, D'Souza AR, Powell CA, Rebelo-Guiomar P, Harbour ME, Ding S, Fearnley IM, Andrews B, Minczuk M. Nucleic Acids Res. 47 10267-10281 (2019)
  23. Paromomycin Reduces Vairimorpha (Nosema)ceranae Infection in Honey Bees but Perturbs Microbiome Levels and Midgut Cell Function. Cho RM, Kogan HV, Elikan AB, Snow JW. Microorganisms 10 1107 (2022)
  24. Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate. Halfon Y, Jimenez-Fernandez A, La Rosa R, Espinosa Portero R, Krogh Johansen H, Matzov D, Eyal Z, Bashan A, Zimmerman E, Belousoff M, Molin S, Yonath A. Proc. Natl. Acad. Sci. U.S.A. 116 22275-22281 (2019)
  25. The shift from early to late types of ribosomes in zebrafish development involves changes at a subset of rRNA 2'-O-Me sites. Ramachandran S, Krogh N, Jørgensen TE, Johansen SD, Nielsen H, Babiak I. RNA 26 1919-1934 (2020)


Quick links