title: New target for inhibition of bacterial RNA polymerase: 'switch region'.
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.
authors.affiliation: Howard Hughes Medical Institute, Waksman Institute, and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Aashish
authors.initials: A
authors.lastname: Srivastava
authors.forename: Meliza
authors.initials: M
authors.lastname: Talaue
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.forename: David
authors.initials: D
authors.lastname: Degen
authors.forename: Richard Y
authors.initials: RY
authors.lastname: Ebright
authors.forename: Elena
authors.initials: E
authors.lastname: Sineva
authors.forename: Anirban
authors.initials: A
authors.lastname: Chakraborty
authors.forename: Sergey Y
authors.initials: SY
authors.lastname: Druzhinin
authors.forename: Sujoy
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Jayanta
authors.initials: J
authors.lastname: Mukhopadhyay
authors.forename: Yon W
authors.initials: YW
authors.lastname: Ebright
authors.forename: Alex
authors.initials: A
authors.lastname: Zozula
authors.forename: Juan
authors.initials: J
authors.lastname: Shen
authors.forename: Sonali
authors.initials: S
authors.lastname: Sengupta
authors.forename: Rui Rong
authors.initials: RR
authors.lastname: Niedfeldt
authors.forename: Cai
authors.initials: C
authors.lastname: Xin
authors.forename: Takushi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Herbert
authors.initials: H
authors.lastname: Irschik
authors.forename: Rolf
authors.initials: R
authors.lastname: Jansen
authors.forename: Stefano
authors.initials: S
authors.lastname: Donadio
authors.forename: Nancy
authors.initials: N
authors.lastname: Connell
authors.forename: Richard H
authors.initials: RH
authors.lastname: Ebright
mesh_terms: D000617:Aminoglycosides / Q000302:isolation & purification / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D000077732:Fidaxomicin; D006801:Humans; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology; D050296:Microbial Viability / Q000187:drug effects
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D007783:Lactones; C532894:corallopyronin A; C096600:ripostatin A; C096601:ripostatin B; C040322:myxopyronin A; C040323:myxopyronin B; D012321:DNA-Directed RNA Polymerases; D000077732:Fidaxomicin