• Architecture of the ribosome RNA-protein machine assembly
• 49 min
  1. High resolution structure of ribosomal subunits RNA/RNA and protein/RNA interactions

  • Prof. Nenad Ban
• 38 min
  2. Assembly of the 30S ribosomal subunit in vitro and in cells

  • Prof. James Williamson
• Decoding and peptide bond formation
• 46 min
  3. How aminoacyl-tRNA synthetases translate the genetic code

  • Dr. Stephen Cusack
• 42 min
  4. The structural basis for how the large ribosomal subunit catalyses peptide bond formation

  • Prof. Thomas Steitz
• 47 min
  5. Elongation of protein synthesis: structural basis of the process of decoding

  • Prof. Marina Rodnina
• Initiation of protein synthesis
• 49 min
  6. The structure-based mechanism of translation initiation in bacteria and eukaryotes

  • Prof. Jeffrey Kieft
• 48 min
  7. Factor independent initiation of protein synthesis by IRES RNAs

  • Prof. Jeffrey Kieft
• Elongation and termination of protein synthesis
• 41 min
  8. Translocation: movement of tRNA and mRNA through the ribosome

  • Prof. Harry Noller
• 31 min
  9. Recoding: getting more out of the message by shifting reading frame and redefining codon meaning

  • Prof. John Atkins
  • Prof. Raymond Gesteland
• Co-translational protein secretion
• 75 min
  10. Mechanism of translocon function: current insights and models

  • Prof. Arnold Driessen
• How antibiotics target the ribosome
• 29 min
  11. Antibiotics that target the 50S ribosome subunit: resistance and other considerations

  • Dr. Joyce Sutcliffe
• 35 min
  12. Antibiotic inhibition of ribosome function

  • Dr. Daniel Wilson
• 45 min
  13. Structure-based drug design targeting infectious disease

  • Dr. Erin Duffy
• Archived Lectures *These may not cover the latest advances in the field
• 26 min
  14. Structural insights into aminoacyl-tRNA delivery by EF-Tu and translocation by EF-G

  • Prof. Joachim Frank
• 21 min
  15. Introduction to the ribosome

  • Prof. Anders Liljas
• 20 min
  16. The structure of the intact ribosome and ribosomal subunit interactions

  • Dr. Jamie H. Doudna Cate
• 42 min
  17. Structural insights into decoding of mRNA by the ribosome

  • Prof. Venki Ramakrishnan
• 63 min
  18. Chemistry of peptide bond formation

  • Prof. Rachel Green
• 49 min
  19. The interaction of antibiotics with the large ribosomal subunit from Haloarcula marismortui

  • Prof. Peter Moore

Printable Handouts

PDF

Navigable Slide Index

1. Introduction
2. Protein synthesis
3. Interference sites for protein synthesis
4. David versus Goliath
5. Drug targets on 16S rRNA
6. 30S-antibiotic structure (1)
7. 30S-antibiotic structure (2)
8. Drug targets on 23S rRNA
9. 50S-antibiotic structures
10. Initiation inhibitors
11. Kasugamycin history
12. 30S-Kasugamycin structure
13. Kasugamycin primary binding site (1)
14. Kasugamycin primary binding site (2)
15. Kasugamycin resistance
16. Alternative conformations for helix 45
17. Indirect resistance mechanism
18. Kasugamycin secondary binding site
19. Kasugamycin: 70S versus 30S
20. Kasugamycin binds in mRNA pathway
21. Kasugamycin inhibits tRNA binding to 30S
22. Mechanism of kasugamycin action
23. Inhibitors of initiation: edeine and pactamycin
24. 30S-edeine structure
25. 30S-pactamycin structure
26. Pactamycin inhibits translocation
27. Relative binding sites of initiation inhibitors
28. Thiostrepton
29. Chemical structure of thiostrepton
30. Thiostrepton binding site on 23S rRNA
31. 50S-thiostrepton structure
32. 50S binding site of thiostrepton
33. Thiostrepton interaction
34. Native L11 position
35. Free versus bound thiostrepton
36. Minimal thiostrepton fragment
37. Interaction of DHP
38. Thiostrepton inhibits EF-G dependent Pi release
39. Cryo-EM of 70S-EF-G complex
40. Stalk base movement upon EF-G binding
41. Thiostrepton allows initial binding of EF-G
42. Thiostrepton prevents EF-G accommodation
43. Thiostrepton resistance in bacteria
44. Thiostrepton resistance in eukaryotes
45. Peptidyltransferase (PTF) inhibitors
46. Binding site of PTF inhibitors on 23S rRNA
47. Inhibition of PTF activity
48. Chemical structure of chloramphenicol
49. 50S-chloramphenicol structure
50. Peptidyltransferase centre
51. Chloramphenicol binding site on 50S
52. Chloramphenicol overlap with A-tRNA
53. Chemical structures of macrolide antibiotics
54. Macrolide binding site on 23S rRNA
55. 50S-telithromycin structure
56. Telithromycin binds in tunnel
57. D50S-Tel versus H50S-Tel
58. D50S-Tel versus D50S-Tel new
59. New D50S-Tel versus H50S-Tel
60. Species specific binding of antibiotics (1)
61. Species-specific binding of antibiotics (2)
62. Summary
63. Bibliography

Topics Covered

• Overview of antibiotics that target the ribosome
• Different mechanisms by which translation initiation inhibitors, such as kasugamycin and edeine, perturb initiator tRNA binding
• Structural insight into how the thiopeptide class of antibiotics, such as thiostrepton and micrococcin, inhibit stable binding of translation factors, such as EF-G, to the ribosome
• Mechanism by which drugs, such as chloramphenicol and macrolides inhibit the peptidyltransferase reaction
• How species specific differences in antibiotic interaction sites between different organisms can have a dramatic influence on drug binding

Links

Series:

• The Mechanisms of Ribosome Function

Categories:

• Biochemistry
• Cell Biology
• Microbiology
• Pharmaceutical Sciences

Therapeutic Areas:

• Infectious Diseases

Talk Citation

Publication History

• Published on May 15, 2008

Financial Disclosures

• Dr. Daniel Wilson has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.