Characterization of molecular interactions between Escherichia coli RNA polymerase and topoisomerase I by molecular simulations

FEBS Lett. 2016 Sep;590(17):2844-51. doi: 10.1002/1873-3468.12321. Epub 2016 Aug 4.

Abstract

Escherichia coli topoisomerase I (EctopoI), a type IA DNA topoisomerase, relaxes the negative DNA supercoiling generated by RNA polymerase (RNAP) during transcription elongation. Due to the lack of structural information on the complex, the exact nature of the RNAP-EctopoI interactions remains unresolved. Herein, we report for the first time, the structure-based modeling of the RNAP-EctopoI interactions using computational methods. Our results predict that the salt bridge as well as hydrogen bond interactions are responsible for the formation and stabilization of the RNAP-EctopoI complex. Our investigations provide molecular insights for understanding how EctopoI interacts with RNAP, a critical step for preventing hypernegative DNA supercoiling during transcription.

Keywords: E. coli topoisomerase I; MD simulations; RNA polymerase; SPR; hydrogen bonds; salt bridge.

Publication types

  • Letter

MeSH terms

  • DNA Topoisomerases, Type I / chemistry*
  • DNA Topoisomerases, Type I / genetics
  • DNA Topoisomerases, Type I / metabolism
  • DNA-Directed RNA Polymerases / chemistry*
  • DNA-Directed RNA Polymerases / genetics
  • DNA-Directed RNA Polymerases / metabolism
  • Escherichia coli / chemistry
  • Escherichia coli / enzymology
  • Hydrogen Bonding
  • Multiprotein Complexes / chemistry*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Protein Binding
  • Protein Conformation
  • Transcription, Genetic*

Substances

  • Multiprotein Complexes
  • DNA-Directed RNA Polymerases
  • DNA Topoisomerases, Type I