TY - JOUR
T1 - New target for inhibition of bacterial RNA polymerase
T2 - 'switch region'
AU - Srivastava, Aashish
AU - Talaue, Meliza
AU - Liu, Shuang
AU - Degen, David
AU - Ebright, Richard Y.
AU - Sineva, Elena
AU - Chakraborty, Anirban
AU - Druzhinin, Sergey Y.
AU - Chatterjee, Sujoy
AU - Mukhopadhyay, Jayanta
AU - Ebright, Yon W.
AU - Zozula, Alex
AU - Shen, Juan
AU - Sengupta, Sonali
AU - Niedfeldt, Rui Rong
AU - Xin, Cai
AU - Kaneko, Takushi
AU - Irschik, Herbert
AU - Jansen, Rolf
AU - Donadio, Stefano
AU - Connell, Nancy
AU - Ebright, Richard H.
N1 - Funding Information:
Preparation of this report was supported by NIH grants GM41376 , AI072766 , and AI90837 , a Global Alliance for TB Drug Development contract, and a Howard Hughes Medical Institute Investigatorship to R.H.E.
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
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U2 - 10.1016/j.mib.2011.07.030
DO - 10.1016/j.mib.2011.07.030
M3 - Review article
C2 - 21862392
AN - SCOPUS:80053908350
SN - 1369-5274
VL - 14
SP - 532
EP - 543
JO - Current Opinion in Microbiology
JF - Current Opinion in Microbiology
IS - 5
ER -