Metal ion and inter-domain interactions as functional networks in E. coli topoisomerase I

Claudia Sissi, Bokun Cheng, Valentina Lombardo, Yuk Ching Tse-Dinh, Manlio Palumbo

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Escherichia coli topoisomerase I (EcTopoI) is a type IA bacterial topoisomerase which is receiving large attention due to its potential application as novel target for antibacterial therapeutics. Nevertheless, a detailed knowledge of its mechanism of action at molecular level is to some extent lacking. This is partly due to the requirement of several factors (metal ions, nucleic acid) to the proper progress of the enzyme catalytic cycle. Additionally, each of them can differently affect the protein structure.Here we assess the role of the different components (DNA, metal ions, protein domains) in a dynamic environment as in solution by monitoring the catalytic as well as the structural properties of EcTopoI.Our results clearly indicated the interaction among these components as functionally relevant and underlined their mutual involvement. Some similarities with other enzymes of the same family emerged (for example DNA prevents divalent metal ions coordination at non selective binding sites). Interestingly, same interactions (C- and N-terminal domain interaction) appear to be peculiar of this bacterial topoisomerase which suggest they could be favorably exploited to the design of selective inhibitors for this class of enzyme.

Original languageEnglish (US)
Pages (from-to)253-260
Number of pages8
JournalGene
Volume524
Issue number2
DOIs
StatePublished - Jul 25 2013

Keywords

  • Circular dichroism
  • Electrophoresis
  • Macromolecule interaction
  • Metal ion
  • Nucleic acid

ASJC Scopus subject areas

  • Genetics

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