The Molecular Basis for Purine Binding Selectivity in the Bacterial ATP Synthase ϵ Subunit

Alexander Krah*, Roland G. Huber, Duncan G.G. McMillan, Peter J. Bond

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

4 Citations (Scopus)

Abstract

The ϵ subunit of ATP synthases has been proposed to regulate ATP hydrolysis in bacteria. Prevailing evidence supports the notion that when the ATP concentration falls below a certain threshold, the ϵ subunit changes its conformation from a non-inhibitory down-state to an extended up-state that then inhibits enzymatic ATP hydrolysis by binding to the catalytic domain. It has been demonstrated that the ϵ subunit from Bacillus PS3 is selective for ATP over other nucleotides, including GTP. In this study, the purine triphosphate selectivity is rationalized by using results from MD simulations and free energy calculations for the R103A/R115A mutant of the ϵ subunit from Bacillus PS3, which binds ATP more strongly than the wild-type protein. Our results are in good agreement with experimental data, and the elucidated molecular basis for selectivity could help to guide the design of novel GTP sensors.

Original languageEnglish
Pages (from-to)3249-3254
Number of pages6
JournalChemBioChem
Volume21
Issue number22
DOIs
Publication statusPublished - 2020

Keywords

  • ATP synthase
  • Bacillus PS3
  • epsilon subunit
  • ligand selectivity
  • molecular dynamics simulations

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