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The Molecular Basis for Purine Binding Selectivity in the Bacterial ATP Synthase ϵ Subunit
Author(s) -
Krah Alexander,
Huber Roland G.,
McMillan Duncan G. G.,
Bond Peter J.
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000291
Subject(s) - protein subunit , gtp' , atp hydrolysis , atp synthase , atp synthase gamma subunit , biochemistry , purine , chemistry , nucleotide , enzyme , adenosine triphosphate , mutant , stereochemistry , atpase , gene
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.