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

Journal article (2020)

Authors

Alexander Krah Korea Institute for Advanced Study, Agency for Science, Technology and Research
Roland G. Huber Agency for Science, Technology and Research
D.G.G. McMillan BT/Biocatalysis - AS
Peter J. Bond National University of Singapore, Agency for Science, Technology and Research
Research Group
BT/Biocatalysis (AS) (TU Delft)
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Published Date

2020

Language

English

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Faculty

Applied Sciences

Department

BT/Biotechnologie

Research Group

BT/Biocatalysis

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.

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