The Molecular Basis for Purine Binding Selectivity in the Bacterial ATP Synthase ϵ Subunit. (4th August 2020)

• Record Type: Journal Article
• Authors: Krah, Alexander; Huber, Roland G.; McMillan, Duncan G. G.; Bond, Peter J.
• Is Part Of: Chembiochem. Volume 21:Number 22(2020)
• Page Start: 3249
• Page End: 3254
• Publication Date: 2020-08-04
• Subjects: ATP synthase -- Bacillus PS3 -- epsilon subunit -- ligand selectivity -- molecular dynamics simulations; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202000291
• Languages: English
• ISSNs: 1439-4227

Abstract

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. Abstract : The ups and downs of purine binding : Nucleotide binding to the bacterial ϵ subunit causes a conformational change from the up‐ to the down‐state. In this study, we clarify the structural and energetic basis of purine binding and the purine selectivity of the ϵ subunit from Bacillus PS3.