1. New target for inhibition of bacterial RNA polymerase: 'switch region'.
- Author
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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, and Ebright RH
- Subjects
- Aminoglycosides isolation & purification, Aminoglycosides pharmacology, Anti-Bacterial Agents isolation & purification, Fidaxomicin, Humans, Lactones isolation & purification, Lactones pharmacology, Microbial Viability drug effects, Anti-Bacterial Agents pharmacology, Bacteria drug effects, Bacteria enzymology, Bacterial Proteins antagonists & inhibitors, DNA-Directed RNA Polymerases antagonists & inhibitors
- Abstract
A new drug target - the 'switch region' - has been identified within bacterial RNA polymerase (RNAP), the enzyme that mediates bacterial RNA synthesis. The new target serves as the binding site for compounds that inhibit bacterial RNA synthesis and kill bacteria. Since the new target is present in most bacterial species, compounds that bind to the new target are active against a broad spectrum of bacterial species. Since the new target is different from targets of other antibacterial agents, compounds that bind to the new target are not cross-resistant with other antibacterial agents. Four antibiotics that function through the new target have been identified: myxopyronin, corallopyronin, ripostatin, and lipiarmycin. This review summarizes the switch region, switch-region inhibitors, and implications for antibacterial drug discovery., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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