Drugs targeting the ribosome

Current Opinion in Structural Biology

Volumn 15, Issue 3 SPEC. ISS., 2005, Pages 355-366

  Hermann, Thomas ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOGLYCOSIDE ANTIBIOTIC AGENT; ANISOMYCIN; ANTIBIOTIC AGENT; ANTIBIOTIC G 418; APRAMYCIN; AZITHROMYCIN; BACTERIAL RNA; BLASTICIDIN S; CETHROMYCIN; CHLORAMPHENICOL DERIVATIVE; CLINDAMYCIN; DALFOPRISTIN; DALFOPRISTIN PLUS QUINUPRISTIN; EP 001304; ERYTHROMYCIN; KETOLIDE; LINEZOLID; MACROLIDE; MIKAMYCIN B; NEAMINE; OXAZOLIDINONE DERIVATIVE; PAROMOMYCIN; PEPTIDYLTRANSFERASE; QUINUPRISTIN; RIBOSOME RNA; SPARSOMYCIN; STREPTOGRAMIN DERIVATIVE; TELITHROMYCIN; TETRACYCLINE DERIVATIVE; TIAMULIN; TOBRAMYCIN; TROLEANDOMYCIN; TYLOSIN; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; BACTERIAL CELL; BACTERIOSTASIS; BACTERIUM MUTANT; BINDING SITE; CELL VIABILITY; DRUG BINDING; DRUG BINDING SITE; DRUG MECHANISM; DRUG STRUCTURE; DRUG TARGETING; FLUORESCENCE ANALYSIS; GENE MUTATION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL; PROTEIN TARGETING; REVIEW; RIBOSOME; RNA ANALYSIS; RNA STRUCTURE; STRUCTURE ACTIVITY RELATION; THREE DIMENSIONAL IMAGING; X RAY CRYSTALLOGRAPHY;

EID: 20444495201     PISSN: 0959440X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.sbi.2005.05.001     Document Type: Review

References (65)

1. E. Cundliffe Antibiotic biosynthesis; some thoughts on "why?" and "how?" R.A. Garrett S.R. Douthwaite A. Liljas A.T. Matheson P.B. Moore H.F. Noller The Ribosome: Structure, Function, Antibiotics and Cellular Interactions 2003 American Society for Microbiology Washington, DC 409 417
2. J.M. Ogle, A.P. Carter, and V. Ramakrishnan Insights into the decoding mechanism from recent ribosome structures Trends Biochem Sci 28 2003 259 266
3. T. Auerbach, A. Bashan, and A. Yonath Ribosomal antibiotics: structural basis for resistance, synergism and selectivity Trends Biotechnol 22 2004 570 576
4. D.J.C. Knowles, N. Foloppe, N.B. Matassova, and A.I.H. Murchie The bacterial ribosome, a promising focus for structure-based drug design Curr Opin Pharmacol 2 2002 501 506
5. Q. Vicens, and E. Westhof RNA as a drug target: the case of aminoglycosides ChemBioChem 4 2003 1018 1023
6. D.E. Brodersen, W.M. Clemons, A.P. Carter, R.J. Morgan-Warren, B.T. Wimberly, and V. Ramakrishnan The structural basis for the action of the antibiotics tetracycline, pactamycin, and hygromycin B on the 30S ribosomal subunit Cell 103 2000 1143 1154
7. M. Pioletti, F. Schlunzen, J. Harms, R. Zarivach, M. Gluhmann, H. Avila, A. Bashan, H. Bartels, T. Auerbach, and C. Jacobi Crystal structures of complexes of the small ribosomal subunit with tetracycline, edeine and IF3 EMBO J 20 2001 1829 1839
8. A.P. Carter, W.M. Clemons, D. Brodersen, R.J. Morgan-Warren, B.T. Wimberly, and V. Ramakrishnan Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics Nature 407 2000 340 348
9. D. Fourmy, M.I. Recht, S.C. Blanchard, and J.D. Puglisi Structure of the A site of Escherichia coli 16S ribosomal RNA complexed with an aminoglycoside antibiotic Science 274 1996 1367 1371
10. Q. Vicens, and E. Westhof Crystal structure of paromomycin docked into the eubacterial ribosomal decoding A site Structure 9 2001 647 658
11. Q. Vicens, and E. Westhof Crystal structure of a complex between the aminoglycoside tobramycin and an oligonucleotide containing the ribosomal decoding a site Chem Biol 9 2002 747 755
12. Q. Vicens, and E. Westhof Crystal structure of geneticin bound to a bacterial 16S ribosomal RNA A site oligonucleotide J Mol Biol 326 2003 1175 1188
13. Q. Vicens, and E. Westhof Molecular recognition of aminoglycoside antibiotics by ribosomal RNA and resistance enzymes: an analysis of X-ray crystal structures Biopolymers 70 2003 42 57
14. S.R. Lynch, R.L. Gonzalez, and J.D. Puglisi Comparison of X-ray crystal structure of the 30S subunit-antibiotic complex with NMR structure of decoding site oligonucleotide-paromomycin complex Structure 11 2003 43 53
15. S. Shandrick, Q. Zhao, Q. Han, B.K. Ayida, M. Takahashi, G.C. Winters, K.B. Simonsen, D. Vourloumis, and T. Hermann Monitoring molecular recognition of the ribosomal decoding site Angew Chem Int Ed Engl 43 2004 3177 3182
16. M. Kaul, C.M. Barbieri, and D.S. Pilch Fluorescence-based approach for detecting and characterizing antibiotic-induced conformational changes in ribosomal RNA: comparing aminoglycoside binding to prokaryotic and eukaryotic ribosomal RNA sequences J Am Chem Soc 126 2004 3447 3453
17. P. Pfister, S. Hobbie, Q. Vicens, E.C. Bottger, and E. Westhof The molecular basis for A-site mutations conferring aminoglycoside resistance: relationship between ribosomal susceptibility and X-ray crystal structures ChemBioChem 4 2003 1078 1088 A systematic and exhaustive analysis of resistance mutations of the ribosomal decoding site in the context of three-dimensional structures of aminoglycoside antibiotic complexes. The analysis precisely illustrates the molecular causes of aminoglycoside resistance induced by target site mutations and provides insight into drug selectivity for the bacterial decoding site.
18. Han Q, Zhao Q, Fish S, Simonsen KB, Vourloumis D, Froelich J, Wall D, Hermann T: Molecular recognition by glycoside pseudo-base pairs and triples in an apramycin-RNA complex. Angew Chem Intl Ed Engl 2005, in press. Crystal structure analysis of the unique aminoglycoside antibiotic apramycin complexed with a ribosomal decoding site oligonucleotide. The structure reveals an unprecedented combination of glycoside pseudo-base pairs and triples formed between sugar moieties of the drug and bases of the RNA target, hinting at a potentially common mechanism of RNA recognition by saccharide natural products.
19. T. Hermann, and Y. Tor RNA as a target for small-molecule therapeutics Expert Opin Ther Patents 15 2005 49 62
20. R.J. Russell, J.B. Murray, G. Lentzen, J. Haddad, and S. Mobashery The complex of a designer antibiotic with a model aminoacyl site of the 30S ribosomal subunit revealed by X-ray crystallography J Am Chem Soc 125 2003 3410 3411
21. B. Francois, J. Szychowski, S.S. Adhikari, K. Pachamuthu, E.E. Swayze, R.H. Griffey, M.T. Migawa, E. Westhof, and S. Hanessian Anti-bacterial aminoglycosides with a modified mode of binding to the ribosomal-RNA decoding site Angew Chem Int Ed Engl 43 2004 6735 6738
22. D. Vourloumis, G.C. Winters, K.B. Simonsen, M. Takahashi, B.K. Ayida, S. Shandrick, Q. Zhao, Q. Han, and T. Hermann Aminoglycoside-hybrid ligands targeting the ribosomal decoding site ChemBioChem 6 2005 58 65
23. M.V. Rodnina, and W. Wintermeyer Peptide bond formation on the ribosome: structure and mechanism Curr Opin Struct Biol 13 2003 334 340
24. M.R. Barbachyn, and C.W. Ford Oxazolidinone structure-activity relationships leading to linezolid Angew Chem Int Ed Engl 42 2003 2010 2023
25. C.C. Zhou, S.M. Swaney, D.L. Shinabarger, and B.J. Stockman 1H nuclear magnetic resonance study of oxazolidinone binding to bacterial ribosomes Antimicrob Agents Chemother 46 2002 625 629
26. J.R. Colca, W.G. McDonald, D.J. Waldon, L.M. Thomasco, R.C. Gadwood, E.T. Lund, G.S. Cavey, W.R. Mathews, L.D. Adams, and E.T. Cecil Cross-linking in the living cell locates the site of action of oxazolidinone antibiotics J Biol Chem 278 2003 21972 21979
27. J.M. Harms, H. Bartels, F. Schlunzen, and A. Yonath Antibiotics acting on the translational machinery J Cell Sci 116 2003 1391 1393
28. J.L. Hansen, P.B. Moore, and T.A. Steitz Structures of five antibiotics bound at the peptidyl transferase center of the large ribosomal subunit J Mol Biol 330 2003 1061 1075 Crystal structure analysis of the H. marismortui 50S ribosomal subunit in complex with the PTC-binding antibiotics anisomycin, sparsomycin, blasticidin S, chloramphenicol and the streptogramin A compound virginiamycin M. This paper illustrates nicely the variety of chemotypes in natural ligands of the PTC.
29. F. Schlunzen, R. Zarivach, J. Harms, A. Bashan, A. Tocilj, R. Albrecht, A. Yonath, and F. Franceschi Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria Nature 413 2001 814 821
30. K.S. Long, and B.T. Porse A conserved chloramphenicol binding site at the entrance to the ribosomal peptide exit tunnel Nucleic Acids Res 31 2003 7208 7215
31. G. Hogenauer, H. Egger, C. Ruf, and B. Stumper Affinity labeling of Escherichia coli ribosomes with a covalently binding derivative of the antibiotic pleuromutilin Biochemistry 20 1981 546 552
32. F. Schlunzen, E. Pyetan, P. Fucini, A. Yonath, and J.M. Harms Inhibition of peptide bond formation by pleuromutilins: the structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with tiamulin Mol Microbiol 54 2004 1287 1294 Crystal structure analysis of the D. radiodurans 50S ribosomal subunit in complex with tiamulin, an exotic diterpenoid antibiotic that binds to the PTC. The structure reveals that bound tiamulin overlaps the streptogramin-A-binding site, a surprisingly hydrophobic cavity that is lined by heterobases of the RNA.
33. J.M. Harms, F. Schlunzen, P. Fucini, H. Bartels, and A. Yonath Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin BMC Biol 2 2004 4 Crystal structure analysis of the D. radiodurans 50S ribosomal subunit in complex with clinically important representatives of the synergistically acting antibiotics streptogramin A and B. The structure suggests that the drugs induce a conformational change in a key nucleotide, which might remain temporarily locked in the altered position after removal of the antibiotics. This provides a rationale for the post-antibiotic effect observed for the streptogramin A and B combination.
34. N.J. Johnston, T.A. Mukhtar, and G.D. Wright Streptogramin antibiotics: mode of action and resistance Curr Drug Targets 3 2002 335 344
35. I. Agmon, M. Amit, T. Auerbach, A. Bashan, D. Baram, H. Bartels, R. Berisio, I. Greenberg, J. Harms, and H.A. Hansen Ribosomal crystallography: a flexible nucleotide anchoring tRNA translocation, facilitates peptide-bond formation, chirality discrimination and antibiotics synergism FEBS Lett 567 2004 20 26
36. J. Lee, M. Kwon, K.H. Lee, S. Jeong, S. Hyun, K.J. Shin, and J. Yu An approach to enhance specificity against RNA targets using heteroconjugates of aminoglycosides and chloramphenicol (or linezolid) J Am Chem Soc 126 2004 1956 1957
37. S. Omura Macrolide Antibiotics 2002 Academic Press San Diego
38. J.L. Hansen, J.A. Ippolito, N. Ban, P. Nissen, P.B. Moore, and T.A. Steitz The structures of four macrolide antibiotics bound to the large ribosomal subunit Mol Cell 10 2002 117 128
39. F. Schluenzen, J.M. Harms, F. Franceschi, H.A. Hansen, H. Bartels, R. Zarivach, and A. Yonath Structural basis for the antibiotic activity of ketolides and azalides Structure 11 2003 329 338 Crystal structure analysis of the D. radiodurans 50S ribosomal subunit in complex with second-generation macrolides, including the clinically important azalide azithromycin and the prototypic ketolide antibiotic cethromycin (ABT-773). The structural data reveal an unexpected secondary binding site for azithromycin, adjacent to the primary site (as described in [38]). For the ketolide, the crystal structure illustrates the role of the synthetic heteroaryl substituent at the 6-position. This is required to maintain the antibacterial activity of this compound class, which lacks the cladinose sugar at the 3-position.
40. ••], this paper illustrates further the molecular recognition of the ribosome by ketolide antibiotics, which rely exclusively on interactions with the rRNA.
41. R. Berisio, F. Schluenzen, J. Harms, A. Bashan, T. Auerbach, D. Baram, and A. Yonath Structural insight into the role of the ribosomal tunnel in cellular regulation Nat Struct Biol 10 2003 366 370 Crystal structure analysis of the D. radiodurans 50S ribosomal subunit in complex with the peracetylated macrolide troleandomycin. Due to the modification of key hydroxyl groups, the antibiotic binds at a unique location, deep in the peptide exit tunnel, and triggers a conformational change in ribosomal protein L22, which has been implicated as a gatekeeper of nascent peptide progression.
42. T. Tenson, M. Lovmar, and M. Ehrenberg The mechanism of action of macrolides, lincosamides and streptogramin B reveals the nascent peptide exit path in the ribosome J Mol Biol 330 2003 1005 1014
43. H. Yoshida, H. Yamamoto, T. Uchiumi, and A. Wada RMF inactivates ribosomes by covering the peptidyl transferase centre and entrance of peptide exit tunnel Genes Cells 9 2004 271 278
44. L. Xiong, Y. Korkhin, and A.S. Mankin Binding site of the bridged macrolides in the Escherichia coli ribosome Antimicrob Agents Chemother 49 2005 281 288
45. P. Pfister, S. Jenni, J. Poehlsgaard, A. Thomas, S. Douthwaite, N. Ban, and E.C. Bottger The structural basis of macrolide-ribosome binding assessed using mutagenesis of 23S rRNA positions 2058 and 2059 J Mol Biol 342 2004 1569 1581 Insightful genetic analysis of the effects of rRNA mutations on the binding of macrolide antibiotics. Data on resistance conferred on a set of 11 macrolides are analyzed in the context of the crystal structures of 50S subunit-antibiotic complexes. Compatibility of genetic and structural data is discussed, and discrepancies in the case of the clinically important macrolide azithromycin are uncovered.
46. P.M. McNicholas, D.J. Najarian, P.A. Mann, D. Hesk, R.S. Hare, K.J. Shaw, and T.A. Black Evernimicin binds exclusively to the 50S ribosomal subunit and inhibits translation in cell-free systems derived from both gram-positive and gram-negative bacteria Antimicrob Agents Chemother 44 2000 1121 1126
47. L. Belova, T. Tenson, L. Xiong, P.M. McNicholas, and A.S. Mankin A novel site of antibiotic action in the ribosome: interaction of evernimicin with the large ribosomal subunit Proc Natl Acad Sci USA 98 2001 3726 3731
48. M. Nishimura, T. Yoshida, M. Shirouzu, T. Terada, S. Kuramitsu, S. Yokoyama, T. Ohkubo, and Y. Kobayashi Solution structure of ribosomal protein L16 from Thermus thermophilus HB8 J Mol Biol 344 2004 1369 1383
49. P.C. Ryan, M. Lu, and D.E. Draper Recognition of the highly conserved GTPase center of 23 S ribosomal RNA by ribosomal protein L11 and the antibiotic thiostrepton J Mol Biol 221 1991 1257 1268
50. G. Lentzen, R. Klinck, N. Matassova, F. Aboul-ela, and A.I. Murchie Structural basis for contrasting activities of ribosome binding thiazole antibiotics Chem Biol 10 2003 769 778
51. G. Rosendahl, and S. Douthwaite The antibiotics micrococcin and thiostrepton interact directly with 23S rRNA nucleotides 1067A and 1095A Nucleic Acids Res 22 1994 357 363
52. Y. Xing, and D.E. Draper Cooperative interactions of RNA and thiostrepton antibiotic with two domains of ribosomal protein L11 Biochemistry 35 1996 1581 1588
53. J. Bower, M. Drysdale, R. Hebdon, A. Jordan, G. Lentzen, N. Matassova, A. Murchie, J. Powles, and S. Roughley Structure-based design of agents targeting the bacterial ribosome Bioorg Med Chem Lett 13 2003 2455 2458
54. S.R. Starck, X. Qi, B.N. Olsen, and R.W. Roberts The puromycin route to assess stereo- and regiochemical constraints on peptide bond formation in eukaryotic ribosomes J Am Chem Soc 125 2003 8090 8091
55. K. Fredrick, and H.F. Noller Catalysis of ribosomal translocation by sparsomycin Science 300 2003 1159 1162
56. J.M. Ogle, F.V. Murphy, M.J. Tarry, and V. Ramakrishnan Selection of tRNA by the ribosome requires a transition from an open to a closed form Cell 111 2002 721 732
57. I.S. Gabashvili, M. Whirl-Carrillo, M. Bada, D.R. Banatao, and R.B. Altman Ribosomal dynamics inferred from variations in experimental measurements RNA 9 2003 1301 1307
58. J. Frank Electron microscopy of functional ribosome complexes Biopolymers 68 2003 223 233
59. S.C. Blanchard, H.D. Kim, R.L. Gonzalez Jr., J.D. Puglisi, and S. Chu tRNA dynamics on the ribosome during translation Proc Natl Acad Sci USA 101 2004 12893 12898
60. M.V. Rodnina, T. Daviter, K. Gromadski, and W. Wintermeyer Structural dynamics of ribosomal RNA during decoding on the ribosome Biochimie 84 2002 745 754
61. W. Wintermeyer, F. Peske, M. Beringer, K.B. Gromadski, A. Savelsbergh, and M.V. Rodnina Mechanisms of elongation on the ribosome: dynamics of a macromolecular machine Biochem Soc Trans 32 2004 733 737
62. S.C. Blanchard, R.L. Gonzalez, H.D. Kim, S. Chu, and J.D. Puglisi tRNA selection and kinetic proofreading in translation Nat Struct Mol Biol 11 2004 1008 1014
63. + aminoglycosides J Mol Biol 346 2004 467 475 The authors used bacterial strains carrying homogenous populations of mutant ribosomes to investigate the molecular basis of decoding site discrimination of the 6′-position in aminoglycoside antibiotics.
64. • ]).
65. P. Pfister, N. Corti, S. Hobbie, C. Bruell, R. Zarivach, A. Yonath, and E.C. Böttger 23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A->G Proc Natl Acad Sci USA 102 2005 5180 5185 An investigation into the interplay of a base pair polymorphism in 23S rRNA with the A2058G point mutation that confers macrolide resistance. The authors demonstrate that subtle structural differences in the rRNA of different organisms may result in functional consequences that determine distinct antibiotic susceptibility.