Identification of novel bacterial RNA polymerase “Switch Region-inhibitors using pharmacophore model based on multi-template and similarity research

详细信息    查看全文

• 作者：Tao Liu (1)
  LuFen He (1)
  Lu Zhou (1)
  QianYing Yi (1)
  HuanHuan Shi (1)
  Xiangyang Tang (2)
  
• 关键词：Bacterial RNA polymerase ; Switch Region ; Pharmacophore model ; Similarity research ; Antibiotics
• 刊名：Medicinal Chemistry Research
• 出版年：2014
• 出版时间：August 2014
• 年：2014
• 卷：23
• 期：8
• 页码：3793-3802
• 全文大小：
• 参考文献：1. Agarwal AK, Johnson AP, Fishwick CWG (2008) Synthesis of de novo designed small-molecule inhibitors of bacterial RNA polymerase. Tetrahedron 64(43):10049-0054. doi:10.1016/j.tet.2008.08.037 CrossRef
  2. Belogurov GA, Vassylyeva MN, Sevostyanova A, Appleman JR, Xiang AX, Lira R, Webber SE, Klyuyev S, Nudler E, Artsimovitch I, Vassylyev DG (2009) Transcription inactivation through local refolding of the RNA polymerase structure. Nature 457(7227):332-35. doi:10.1038/nature07510 CrossRef
  3. Borukhov Sergei, Konstantin (2002) Role of the RNA polymerase sigma subunit in transcription initiation. Res Microbiol 153:557-62 CrossRef
  4. Buurman ET, Foulk MA, Gao N, Laganas VA, McKinney DC, Moustakas DT, Rose JA, Shapiro AB, Fleming PR (2012) Novel rapidly diversifiable antimicrobial RNA polymerase Switch Region inhibitors with confirmed mode of action in Haemophilus influenzae. J Bacteriol 194(20):5504-512. doi:10.1128/JB.01103-12 CrossRef
  5. Campbell EA, Westblade LF, Darst SA (2008) Regulation of bacterial RNA polymerase sigma factor activity: a structural perspective. Curr Opin Microbiol 11(2):121-27. doi:10.1016/j.mib.02.016 CrossRef
  6. Chakraborty A, Wang D, Ebright YW, Korlann Y, Kortkhonjia E, Kim T, Chowdhury S, Wigneshweraraj S, Irschik H, Jansen R, Nixon BT, Knight J, Weiss S, Ebright RH (2012) Opening and closing of the bacterial RNA polymerase clamp. Science 337(6094):591-95. doi:10.1126/science.1218716 CrossRef
  7. Chen X, Reynolds CH (2002) Performance of similarity measures in 2D fragment-based similarity searching: comparison of structural descriptor and similarity coefficients. J Chem Inf Comput Sci 42:1407-414 CrossRef
  8. Darst SA (2001) Bacterial RNA polymerase. Curr Opin Struct Biol 2001(11):155-62 CrossRef
  9. Darst SA (2004) New inhibitors targeting bacterial RNA polymerase. Trends Biochem Sci 29(4):159-60. doi:10.1016/j.tibs.2004.02.005 CrossRef
  10. Doundoulakis T, Xiang AX, Lira R, Agrios KA, Webber SE, Sisson W, Aust RM, Shah AM, Showalter RE, Appleman JR, Simonsen KB (2004) Myxopyronin B analogs as inhibitors of RNA. polymerase, synthesis and biological evaluation. Bioorg Med Chem Lett 14(22):5667-672. doi:10.1016/j.bmcl.2004.08.045 CrossRef
  11. Ebright R, Ebright Y (2012) Antibacterial agents: high-potency myxopyronin derivatives. PCT/US11/52015 (filed 9/15/2011; pending).
  12. Feklistov A, Darst SA (2011) Structural basis for promoter-10 element recognition by the bacterial RNA polymerase sigma subunit. Cell 147(6):1257-269. doi:10.1016/j.cell.2011.10.041 CrossRef
  13. Iyer LM, Koonin EV, Aravind L (2004) Evolution of bacterial RNA polymerase: implications for large-scale bacterial phylogeny, domain accretion, and horizontal gene transfer. Gene 335:73-8. doi:10.1016/j.gene.2004.03.017 CrossRef
  14. James E, Liu M, Sheppard C, Mekler V, Camara B, Liu B, Simpson P, Cota E, Severinov K, Matthews S, Wigneshweraraj S (2012) Structural and mechanistic basis for the inhibition of Escherichia coli RNA polymerase by T7 Gp2. Mol Cell 47(5):755-66 10.1016/j. mol cel.2012.06.013 CrossRef
  15. Li Y-S, Zhou L, Ma X, Song H, Tang X-Y (2011) Pharmacophore modeling and structure-based virtual screening for a novel “switch region-target of bacterial RNA polymerase. Med Chem Res 21(5):642-52. doi:10.1007/s00044-011-9567-7 CrossRef
  16. Lira R, Xiang AX, Doundoulakis T, Biller WT, Agrios KA, Simonsen KB, Webber SE, Sisson W, Aust RM, Shah AM, Showalter RE, Banh VN, Steffy KR, Appleman JR (2007) Syntheses of novel myxopyronin B analogs as potential inhibitors of bacterial RNA polymerase. Bioorg Med Chem Lett 17(24):6797-800. doi:10.1016/j.bmcl.2007.10.017 CrossRef
  17. Mukhopadhyay J, Das K, Ismail S, Koppstein D, Jang M, Hudson B, Sarafianos S, Tuske S, Patel J, Jansen R, Irschik H, Arnold E, Ebright RH (2008) The RNA polymerase “Switch Region-is a target for inhibitors. Cell 135(2):295-07. doi:10.1016/j.cell.2008.09.033 CrossRef
  18. Richard H, Bright E (2000) RNA polymerase: structural similarities between bacterial RNA polymerase and eukaryotic RNA polymerase II. J Mol Biol 304:687-98. doi:10.1006/jmbi.4309 CrossRef
  19. Saecker RM, Record MT Jr (2011) Dehaseth PL (2011) Mechanism of bacterial transcription initiation: RNA polymerase—promoter binding, isomerization to initiation-competent open complexes, and initiation of RNA synthesis. J Mol Biol 412(5):754-71. doi:10.1016/j.jmb.01.018 CrossRef
  20. Sekine S, Tagami S, Yokoyama S (2012) Structural basis of transcription by bacterial and eukaryotic RNA polymerases. Curr Opin Struct Biol 22(1):110-18. doi:10.1016/j.sbi.2011.11.006 CrossRef
  21. Srivastava A, Talaue M, Liu S, Degen D, Ebright RY, Sineva E, Chakraborty A, Druzhinin SY, Chatterjee S, Mukhopadhyay J, Ebright YW, Zozula A, Shen J, Sengupta S, Niedfeldt RR, Xin C, Kaneko T, Irschik H, Jansen R, Donadio S, Connell N, Ebright RH (2011) New target for inhibition of bacterial RNA polymerase: ‘switch region- Curr Opin Microbiol 14(5):532-43. doi:10.1016/j.mib.2011.07.030 CrossRef
  22. Tuske S, Sarafianos SG, Wang X, Hudson B, Sineva E, Mukhopadhyay J, Birktoft JJ, Leroy O, Ismail S, Clark AD Jr, Dharia C, Napoli A, Laptenko O, Lee J, Borukhov S, Ebright RH, Arnold E (2005) Inhibition of bacterial RNA polymerase by streptolydigin: stabilization of a straight-bridge-helix active-center conformation. Cell 122(4):541-52. doi:10.1016/j.cell.2005.07.017 CrossRef
  23. Yakushiji F, Miyamoto Y, Kunoh Y, Okamoto R, Nakaminami H, Yamazaki Y, Noguchi N, Hayashi Y (2013) Novel hybrid-type antimicrobial agents targeting the Switch Region of bacterial RNA polymerase. ACS Med Chem Lett 4(2):220-24. doi:10.1021/ml300350p CrossRef
  
• 作者单位：Tao Liu (1)
  LuFen He (1)
  Lu Zhou (1)
  QianYing Yi (1)
  HuanHuan Shi (1)
  Xiangyang Tang (2)
  
  1. College of Chemical Engineering, Sichuan University, Chengdu, 610065, Sichuan, People’s Republic of China
  2. College of Computer Science, Southwest University for Nationalities, Chengdu, 610041, Sichuan, People’s Republic of China
  
• ISSN：1554-8120

文摘

Bacterial RNA polymerase, which is a complex molecular machine for RNA synthesis in all cellular organisms, appears to be a new discovered and potential protein. Switch Region of bacterial RNA polymerase turns out to be an ideal target for antibiotics in consequence of highly conserved in gram-positive/negative bacterial and non-conserved in human RNAP. Present study collected recently discovered bacterial RNAP inhibitors and generated a pharmacophore query in combination with similarity research for new antibiotics identification. The generated query is consisted of three features: one hydrophobic site and two acceptor atoms. Then, pharmacophore and similarity research as two different strategies were used against to 1,623,646 compounds from ZINC database. Finally, ten compounds were filtered out as potential antibiotics. This work could be less limitation in various scaffold research and more accuracy in antibiotics discovery by applying novel inhibitors.