Structures of RNA polymerase-antibiotic complexes

Current Opinion in Structural Biology

Volumn 19, Issue 6, 2009, Pages 715-723

  Ho, Mary X ^a,b   Hudson, Brian P ^a,b   Das, Kalyan ^a,b   Arnold, Eddy ^a,b   Ebright, Richard H ^b,c,d  

^a RUTGERS UNIVERSITY   (United States)

^b State University of New Jersey   (United States)

^c HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^d RUTGERS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT; BACTERIAL ENZYME; MYXOPYRONIN; RIFABUTIN; RIFAMPICIN; RIFAMYCIN DERIVATIVE; RIFAPENTINE; RNA POLYMERASE; SORANGICIN; STREPTOLYDIGIN; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; COMPUTER MODEL; CRYSTAL STRUCTURE; DNA STRAND; DRUG BINDING; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG TARGETING; ENZYME INHIBITION; ENZYME STRUCTURE; NONHUMAN; PRIORITY JOURNAL; REVIEW; STRUCTURAL HOMOLOGY; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ANTI-BACTERIAL AGENTS; BACTERIA; DNA-DIRECTED RNA POLYMERASES; MODELS, MOLECULAR; PROTEIN BINDING; SEQUENCE HOMOLOGY, AMINO ACID;

BACTERIA (MICROORGANISMS);

EID: 70549114083     PISSN: 0959440X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.sbi.2009.10.010     Document Type: Review

References (55)

1. Chopra I. Bacterial RNA polymerase: a promising target for the discovery of new antimicrobial agents. Curr Opin Investig Drugs 8 (2007) 600-607
2. Darst S.A. New inhibitors targeting bacterial RNA polymerase. Trends Biochem Sci 29 (2004) 159-160
3. Villain-Guillot P., Bastide L., Gualtieri M., and Leonetti J. Progress in targeting bacterial transcription. Drug Discov Today 12 (2007) 200-208
4. Wehrli W. Ansamycins: chemistry, biosynthesis and biological activity. Top Curr Chem 72 (1977) 21-49
5. Floss H.G., and Yu T.W. Rifamycin-mode of action, resistance, and biosynthesis. Chem Rev 105 (2005) 621-632
6. Campbell E.A., Korzheva N., Mustaev A., Murakami K., Nair S., Goldfarb A., and Darst S.A. Structural mechanism for rifampicin inhibition of bacterial RNA polymerase. Cell 104 (2001) 901-912
7. Artsimovitch I., Vassylyeva M.N., Svetlov D., Svetlov V., Perederina A., Igarashi N., Matsugaki N., Wakatsuki S., Tahirov T.H., and Vassylyev D.G. Allosteric modulation of the RNA polymerase catalytic reaction is an essential component of transcription control by rifamycins. Cell 122 (2005) 351-363
8. 2+ ion.
9. Vassylyev D.G., Vassylyeva M.N., Perederina A., Tahirov T.H., and Artsimovitch I. Structural basis for transcription elongation by bacterial RNA polymerase. Nature 448 (2007) 157-162
10. McClure W.R., and Cech C.L. On the mechanism of rifampicin inhibition of RNA synthesis. J Biol Chem 253 (1978) 8949-8956
11. Xu M., Zhou Y., Goldstein B., and Jin D. Cross-resistance of Escherichia coli RNA polymerases conferring rifampin resistance to different antibiotics. J Bacteriol 187 (2005) 2783-2792
12. Ovchinnikov Y.A., Monastyrskaya G.S., Guriev S.O., Kalinina N.F., Sverdlov E.D., Gragerov A.I., Bass I.A., Kiver I.F., Moiseyeva E.P., Igumnov V.N., et al. RNA polymerase rifampicin resistance mutations in Escherichia coli: sequence changes and dominance. Mol Gen Genet 190 (1983) 344-348
13. Lisitsyn N.A., Gur'ev S.O., Sverdlov E.D., Moiseeva E.P., and Nikiforov V.G. Nucleotide substitutions in the rpoB gene leading to rifampicin resistance of E. coli RNA polymerase. Bioorg Khim 10 (1984) 127-128
14. Jin D.J., and Gross C.A. Mapping and sequencing of mutations in the Escherichia coli rpoB gene that lead to rifampicin resistance. J Mol Biol 202 (1988) 45-58
15. Severinov K., Soushko M., Goldfarb A., and Nikiforov V. Rifampicin region revisited. New rifampicin-resistant and streptolydigin-resistant mutants in the beta subunit of Escherichia coli RNA polymerase. J Biol Chem 268 (1993) 14820-14825
16. Ramaswamy S., and Musser J. Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Tuberc Lung Dis 79 (1998) 3-29
17. Jansen R., Wray V., Irschik H., Reichenbach H., and Hofle G. Isolation and spectroscopic structure elucidation of sorangicin A, a new type of macrolide-polyether antibiotic from gliding bacteria. Tetrah Lett 26 (1985) 6031-6034
18. Irschik H., Jansen R., Gerth K., Hofle G., and Reichenbach H. The sorangicins: novel and powerful inhibitors of eubacterial RNA polymerase isolated from myxobacteria. J Antibiot (Tokyo) 40 (1987) 7-13
19. Smith III A.B., Dong S., Brenneman J.B., and Fox R.J. Total synthesis of (+)-sorangicin A. J Am Chem Soc 131 (2009) 12109-12111
20. Campbell E.A., Pavlova O., Zenkin N., Leon F., Irschik H., Jansen R., Severinov K., and Darst S.A. Structural, functional, and genetic analysis of sorangicin inhibition of bacterial RNA polymerase. EMBO J 24 (2005) 674-682
21. Rommele G., Wirz G., Solf R., Vosbeck K., Gruner J., and Wehrli W. Resistance of Escherichia coli to rifampicin and sorangicin A-a comparison. J Antibiot (Tokyo) 43 (1990) 88-91
22. O'Neill A., Oliva B., Storey C., Hoyle A., Fishwick C., and Chopra I. RNA polymerase inhibitors with activity against rifampin-resistant mutants of Staphylococcus aureus. Antimicrob Agents Chemother 44 (2000) 3163-3166
23. Das K., Clark Jr. A.D., Lewi P.J., Heeres J., De Jonge M.R., Koymans L.M., Vinkers H.M., Daeyaert F., Ludovici D.W., Kukla M.J., et al. Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. J Med Chem 47 (2004) 2550-2560
24. Siddhikol C., Erbstoeszer J.W., and Weisblum B. Mode of action of streptolydigin. J Bacteriol 99 (1969) 151-155
25. Cassani G., Burgess R.R., Goodman H.M., and Gold L. Inhibition of RNA polymerase by streptolydigin. Nat New Biol 230 (1971) 197-200
26. McClure W.R. On the mechanism of streptolydigin inhibition of Escherichia coli RNA polymerase. J Biol Chem 255 (1980) 1610-1616
27. Heisler L.M., Suzuki H., Landick R., and Gross C.A. Four contiguous amino acids define the target for streptolydigin resistance in the beta subunit of Escherichia coli RNA polymerase. J Biol Chem 268 (1993) 25369-25375
28. Severinov K., Markov D., Severinova E., Nikiforov V., Landick R., Darst S.A., and Goldfarb A. Streptolydigin-resistant mutants in an evolutionarily conserved region of the beta' subunit of Escherichia coli RNA polymerase. J Biol Chem 270 (1995) 23926-23929
29. Yang X., and Price C.W. Streptolydigin resistance can be conferred by alterations to either the beta or beta' subunits of Bacillus subtilis RNA polymerase. J Biol Chem 270 (1995) 23930-23933
30. Tuske S., Sarafianos S.G., Wang X., Hudson B., Sineva E., Mukhopadhyay J., Birktoft J.J., Leroy O., Ismail S., Clark Jr. A.D., et al. Inhibition of bacterial RNA polymerase by streptolydigin: stabilization of a straight-bridge-helix active-center conformation. Cell 122 (2005) 541-552
31. Temiakov D., Zenkin N., Vassylyeva M.N., Perederina A., Tahirov T.H., Kashkina E., Savkina M., Zorov S., Nikiforov V., Igarashi N., et al. Structural basis of transcription inhibition by antibiotic streptolydigin. Mol Cell 19 (2005) 655-666
32. Vassylyev D.G., Vassylyeva M.N., Zhang J., Palangat M., Artsimovitch I., and Landick R. Structural basis for substrate loading in bacterial RNA polymerase. Nature 448 (2007) 163-168
33. Wang D., Bushnell D.A., Westover K.D., Kaplan C.D., and Kornberg R.D. Structural basis of transcription: role of the trigger loop in substrate specificity and catalysis. Cell 127 (2006) 941-954
34. Toulokhonov I., Zhang J., Palangat M., and Landick R. A central role of the RNA polymerase trigger loop in active-site rearrangement during transcriptional pausing. Mol Cell 27 (2007) 406-419
35. Brueckner F., Ortiz J., and Cramer P. A movie of the RNA polymerase nucleotide addition cycle. Curr Opin Struct Biol 19 (2009) 294-299
36. Irschik H., Gerth K., Hofle G., Kohl W., and Reichenbach H. The myxopyronins, new inhibitors of bacterial RNA synthesis from Myxococcus fulvus (Myxobacterales). J Antibiot (Tokyo) 36 (1983) 1651-1658
37. Kohl W., Irschik H., Reichenbach H., and Hoefle G. Antibiotics from gliding bacteria: myxopyronin A and myxopyronin B, two novel antibiotics from Myxococcus fulvus strain Mx f50. Liebigs Annalen Der Chemie (1983) 1656-1667
38. Hu T., Schaus J.V., Lam K., Palfreyman M.G., Wuonola M., Gustafson G., and Panek J.S. Total synthesis and preliminary antibacterial evaluation of the RNA polymerase inhibitors (+/-)-myxopyronin A and B. J Org Chem 63 (1998) 2401-2406
39. Mukhopadhyay J., Das K., Ismail S., Koppstein D., Jang M., Hudson B., Sarafianos S., Tuske S., Patel J., Jansen R., et al. The RNA polymerase 'switch region' is a target for inhibitors. Cell 135 (2008) 295-307. This paper reports the target, biochemical basis, and structural basis of inhibition of RNAP by Myx. The paper establishes that Myx interacts with the RNAP switch region - the hinge that mediates opening and closing of the RNAP active-center cleft - and that Myx prevents formation of a catalytically competent RNAP-promoter open complex. The paper reports a crystal structure that defines contacts between Myx and RNAP and defines effects of Myx on RNAP conformation. The paper further reports that the antibiotics corallopyronin and ripostatin function through the same target and same mechanism. The authors propose that Myx inhibits RNAP by preventing opening of the RNAP active-center cleft to permit entry and unwinding of promoter DNA during transcription initation.
40. Belogurov G.A., Vassylyeva M.N., Sevostyanova A., Appleman J.R., Xiang A.X., Lira R., Webber S.E., Klyuyev S., Nudler E., Artsimovitch I., et al. Transcription inactivation through local refolding of the RNA polymerase structure. Nature 457 (2009) 332-335. This paper reports a crystal structure of the RNAP-Myx complex and reports results of DNase-I and permanganate DNA-footprinting experiments with RNAP-Myx complexes. The results confirm that Myx interacts with the RNAP switch region and that Myx prevents formation of a catalytically competent RNAP-promoter open complex. The results indicate that Myx traps an RNAP-promoter complex in which the upstream portion, but not the downstream portion, of the transcription-bubble region of the promoter is unwound. The authors propose that Myx inhibits RNAP by interfering with interactions between RNAP and the downstream portion of the transcription-bubble region of the promoter.
41. Cramer P., Bushnell D., and Kornberg R. Structural basis of transcription: RNA polymerase II at 2.8 angstrom resolution. Science 292 (2001) 1863-1876
42. Cramer P. Multisubunit RNA polymerases. Curr Opin Struct Biol 12 (2002) 89-97
43. Gnatt A., Cramer P., Fu J., Bushnell D., and Kornberg R. Structural basis of transcription: an RNA polymerase II elongation complex at 3.3 Å resolution. Science 292 (2001) 1876-1882
44. Doundoulakis T., Xiang A.X., Lira R., Agrios K.A., Webber S.E., Sisson W., Aust R.M., Shah A.M., Showalter R.E., Appleman J.R., et al. Myxopyronin B analogs as inhibitors of RNA polymerase, synthesis and biological evaluation. Bioorg Med Chem Lett 14 (2004) 5667-5672
45. Das K., Lewi P.J., Hughes S.H., and Arnold E. Crystallography and the design of anti-AIDS drugs: conformational flexibility and positional adaptability are important in the design of non-nucleoside HIV-1 reverse transcriptase inhibitors. Prog Biophys Mol Biol 88 (2005) 209-231
46. Vassylyev D.G., Sekine S., Laptenko O., Lee J., Vassylyeva M.N., Borukhov S., and Yokoyama S. Crystal structure of a bacterial RNA polymerase holoenzyme at 2.6 Å resolution. Nature 417 (2002) 712-719
47. Zhang G., Campbell E.A., Minakhin L., Richter C., Severinov K., and Darst S.A. Crystal structure of Thermus aquaticus core RNA polymerase at 3.3 Å resolution. Cell 98 (1999) 811-824
48. Murakami K., Masuda S., and Darst S. Structural basis of transcription initiation: RNA polymerase holoenzyme at 4 Å resolution. Science 296 (2002) 280-1284
49. Murakami K., Masuda S., Campbell E., Muzzin O., and Darst S. Structural basis of transcription initiation: an RNA polymerase holoenzyme-DNA complex. Science 296 (2002) 1285-1290
50. Irschik H., Jansen R., Hofle G., Gerth K., and Reichenbach H. The corallopyronins, new inhibitors of bacterial RNA synthesis from Myxobacteria. J Antibiot (Tokyo) 38 (1985) 145-152
51. Jansen R., Irschik H., Reichenbach H., and Hofle G. Antibiotics from gliding bacteria. Corallopyronin A, corallopyronin B, and corallopyronin C-three novel antibiotics from Corallococcus coralloides, Cc C127 (Myxobacterales). Liebigs Annalen Der Chemie (1985) 822-836
52. Augustiniak H., Irschik H., Reichenbach H., and Hofle G. Antibiotics from gliding bacteria: Ripostatin A, B, and C-isolation and structure elucidation of novel metabolites from Sorangium cellulosum. Liebigs Annalen Der Chemie (1996) 1657-1663
53. Irschik H., Augustiniak H., Gerth K., Hofle G., and Reichenbach H. The ripostatins, novel inhibitors of eubacterial RNA polymerase isolated from myxobacteria. J Antibiot (Tokyo) 48 (1995) 787-792
54. Šali A., and Blundell T.L. Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234 (1993) 779-815
55. Shen M.-Y., and Šali A. Statistical potential for assessment and prediction of protein structures. Protein Sci 15 (2006) 2507-2524