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Abstract

Complete crystallographic data sets of complexes of D50S with SB-571519, SB-280080, and retapamulin (SB-275833) yielded electron density maps at 3.50, 3.56, and 3.66 Å resolution, respectively, in which the location and conformation of each of the three bound compounds were unambiguously resolved. Grouped occupancy refinement yielded a value of approximately 1.0 for all three compounds, confirming that they are quantitatively bound, in accord with the high binding affinity observed in a competitive ribosome-binding assay by using a radiolabeled pleuromutilin derivative.

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References

  1. Yan K, Madden L, Choudhry AE, Voigt CS, Copeland RA, Gontarek RR (2006) Biochemical characterization of the interactions of the novel pleuromutilin derivative retapamulin with bacterial ribosomes. Antimicrob Agents Chemother 50(11):3875–3881

    Article  CAS  PubMed  Google Scholar 

  2. Schluenzen F, Pyetan E, Fucini P, Yonath A, Harms J (2004) Inhibition of peptide bond formation by pleuromutilins: the structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with tiamulin. Mol Microbiol 54(5):1287–1294

    Article  CAS  Google Scholar 

  3. Gindulyte A, Bashan A, Agmon I, Massa L, Yonath A, Karle J (2006) The transition state for formation of the peptide bond in the ribosome. Proc Natl Acad Sci U S A 103(36):13327–13332

    Article  CAS  PubMed  Google Scholar 

  4. Egger H, Reinshagen H (1976) New pleuromutilin derivatives with enhanced antimicrobial activity. II. Structure–activity correlations. J Antibiot (Tokyo) 29(9):923–927

    CAS  Google Scholar 

  5. Agmon I, Amit M, Auerbach T, Bashan A, Baram D, Bartels H, Berisio R, Greenberg I, Harms J, Hansen HA, Kessler M, Pyetan E, Schluenzen F, Sittner A, Yonath A, Zarivach R (2004) Ribosomal crystallography: a flexible nucleotide anchoring tRNA translocation, facilitates peptide-bond formation, chirality discrimination and antibiotics synergism. FEBS Lett 567(1):20–26

    Article  CAS  PubMed  Google Scholar 

  6. Bashan A, Zarivach R, Schluenzen F, Agmon I, Harms J, Auerbach T, Baram D, Berisio R, Bartels H, Hansen HA, Fucini P, Wilson D, Peretz M, Kessler M, Yonath A (2003) Ribosomal crystallography: peptide bond formation and its inhibition. Biopolymers 70(1):19–41

    Article  CAS  PubMed  Google Scholar 

  7. Harms J, Schluenzen F, Zarivach R, Bashan A, Gat S, Agmon I, Bartels H, Franceschi F, Yonath A (2001) High resolution structure of the large ribosomal subunit from a mesophilic eubacterium. Cell 107(5):679–688

    Article  CAS  PubMed  Google Scholar 

  8. Schuwirth BS, Borovinskaya MA, Hau CW, Zhang W, Vila-Sanjurjo A, Holton JM, Cate JHD (2005) Structures of the bacterial ribosome at 3.5 Å resolution. Science 310(5749):827–834

    Article  CAS  PubMed  Google Scholar 

  9. Selmer M, Dunham CM, Murphy FVt, Weixlbaumer A, Petry S, Kelley AC, Weir JR, Ramakrishnan V (2006) Structure of the 70S ribosome complexed with mRNA and tRNA. Science 313(5795):1935–1942

    Article  CAS  PubMed  Google Scholar 

  10. Bosling J, Poulsen SM, Vester B, Long KS (2003) Resistance to the peptidyl transferase inhibitor tiamulin caused by mutation of ribosomal protein l3. Antimicrob Agents Chemother 47(9):2892–2896

    Article  CAS  PubMed  Google Scholar 

  11. Pringle M, Poehlsgaard J, Vester B, Long KS (2004) Mutations in ribosomal protein L3 and 23S ribosomal RNA at the peptidyl transferase centre are associated with reduced susceptibility to tiamulin in Brachyspira spp. isolates. Mol Microbiol 54(5):1295–1306

    Article  CAS  PubMed  Google Scholar 

  12. Sato NS, Hirabayashi N, Agmon I, Yonath A, Suzuki T (2006) Comprehensive genetic selection revealed essential bases in the peptidyl-transferase center. Proc Natl Acad Sci U S A 103(42):15386–15391

    Article  CAS  PubMed  Google Scholar 

  13. Schluenzen F, Zarivach R, Harms J, Bashan A, Tocilj A, Albrecht R, Yonath A, Franceschi F (2001) Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature 413(6858):814–821

    Article  Google Scholar 

  14. Harms J, Schluenzen F, Fucini P, Bartels H, Yonath A (2004) Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin. BMC Biol 2(1):4;1–10

    Google Scholar 

  15. Auerbach T, Mermershtain I, Davidovich C, Bashan A, Belousoff M, Wekselman I, Zimmerman E, Xiong L, Klepacki D, Arakawa K, Kinashi H, Mankin AS, Yonath A (2010) The structure of ribosome–lankacidin complex reveals ribosomal sites for synergistic antibiotics. Proc Natl Acad Sci U S A 107(5):1983–1988

    Article  CAS  PubMed  Google Scholar 

  16. Auerbach T, Mermershtain I, Bashan A, Davidovich C, Rosenberg H, Sherman DH, Yonath A (2009) Structural basis for the antibacterial activity of the 12-membered-ring mono-sugar macrolide methymycin. Biotechnolog 84:24–35

    Google Scholar 

  17. Agmon I, Bashan A, Zarivach R, Yonath A (2005) Symmetry at the active site of the ribosome: structural and functional implications. Biol Chem 386(9):833–844

    Article  CAS  PubMed  Google Scholar 

  18. Ippolito JA, Kanyo ZF, Wang D, Franceschi FJ, Moore PB, Steitz TA, Duffy EM (2008) Crystal structure of the oxazolidinone antibiotic linezolid bound to the 50S ribosomal subunit. J Med Chem 51(12):3353–3356

    Article  CAS  PubMed  Google Scholar 

  19. Agmon I, Auerbach T, Baram D, Bartels H, Bashan A, Berisio R, Fucini P, Hansen HA, Harms J, Kessler M, Peretz M, Schluenzen F, Yonath A, Zarivach R (2003) On peptide bond formation, translocation, nascent protein progression and the regulatory properties of ribosomes. Eur J Biochem 270(12):2543–2556

    Article  CAS  PubMed  Google Scholar 

  20. Christopher WS (1998) RNA:protein interactions: a practical approach, 1st edn. Oxford University Press, Oxford

    Google Scholar 

  21. Cheong C, Varani G, Tinoco I Jr (1990) Solution structure of an unusually stable RNA hairpin, 5’GGAC(UUCG)GUCC. Nature 346(6285):680–682

    Article  CAS  PubMed  Google Scholar 

  22. Tuerk C, Gauss P, Thermes C, Groebe DR, Gayle M, Guild N, Stormo G, d’Aubenton-Carafa Y, Uhlenbeck OC, Tinoco I Jr et al (1988) CUUCGG hairpins: extraordinarily stable RNA secondary structures associated with various biochemical processes. Proc Natl Acad Sci U S A 85(5):1364–1368

    Article  CAS  PubMed  Google Scholar 

  23. Nissen P, Ippolito JA, Ban N, Moore PB, Steitz TA (2001) RNA tertiary interactions in the large ribosomal subunit: the A-minor motif. Proc Natl Acad Sci U S A 98(9):4899–4903

    Article  CAS  PubMed  Google Scholar 

  24. Knapp G (1989) Enzymatic approaches to probing of RNA secondary and tertiary structure. Methods Enzymol 180:192–212

    Article  CAS  PubMed  Google Scholar 

  25. Linnstaedt SD, Kasprzak WK, Shapiro BA, Casey JL (2006) The role of a metastable RNA secondary structure in hepatitis delta virus genotype III RNA editing. RNA 12(8):1521–1533

    Article  CAS  PubMed  Google Scholar 

  26. Zuker M (1989) On finding all suboptimal foldings of an RNA molecule. Science 244(4900):48–52

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Chen Davidovich .

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Davidovich, C. (2011). Results. In: Targeting Functional Centers of the Ribosome. Springer Theses. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-16931-1_3

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