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Intrinsically disordered proteins and intrinsically disordered regions are implicated in many biological functions and associated with many diseases, but their conformational characterizations are challenging. The disordered β6/β7 loop of Staphylococcus aureus sortase A is involved in the binding of both sorting signals and calcium. Calcium binding allosterically activates the enzyme, but the detailed mechanism has been unclear. Here we adapted the replica exchange with solute tempering method to sample the conformations of the β6/β7 loop, in apo form and in three liganded forms (bound with a sorting signal or calcium or both). The extensive molecular dynamics simulations yield atomic details of the disordered-to-order transition of the loop and suggest a mechanism for allosteric activation: calcium binding results in partial closure and ordering of the loop, thereby leading to preorganization of the binding pocket for the sorting signal. The approach has general applicability to the study of intrinsically disordered regions.
This article was published in the following journal.
Name: Biophysical journal
Various biophysical methods have provided evidence of a second substrate binding site in the well-studied cytochrome P450cam although the location and biological relevance of this site has remained el...
The allosteric activation of the intrinsically disordered enzyme Staphylococcus aureus sortase A is initiated via binding of a Ca2+ ion. Although Ca2+ binding was shown to initiate structural changes ...
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