Streptococcus pneumoniae (S. pneumoniae) is the world’s foremost bacterial pathogen. Diseases arising from S. pneumoniae infections are responsible for more than 1 million deaths every year with an economic health burden of more than US$4 billion annually. Essential to the colonization of S. pneumoniae is its ability to acquire essential nutrients from the host environment, including trace metals such as zinc (Zn) [1]. In S. pneumoniae Zn is acquired by the ABC transporter AdcCB and the Zn-binding protein AcdA [2]. The AdcCBA permease complex acts in concert to facilitate unidirectional Zn import into the bacterial cytosol. Here we sought to examine the conformational landscape of AdcA in solution during its interaction with Zn.
In this study we used four (4)-pulse Double Electron Electron Resonance (DEER) with spin-labelled AdcA. Here, we measured distances between distinct residues of the protein in the presence and absence of Zn. We then combined this approach with Molecular Dynamics simulations of AcdA to generate a series potential conformations sampled by the protein. Here, we will discuss the comparison of the experimental DEER data with simulation data and its use in defining the solution structure of AdcA in the presence and absence of its cognate ligand.