A dynamics study of the A-chain of ricin by terahertz vibrational calculation and normal modes analysis

We studied the terahertz (THz) spectroscopy and low frequency normal modes of both apo- and holo- (adenosine monophosphate (AMP)-bound) ricin-A-chain (RTA) as a means to understand the dynamical changes that RTA undergoes upon substrate binding. The calculated THz spectra of apo- and holo-RTAs demonstrated a general intensity suppression upon substrate binding, which is attributed to the reduced number of collective motion in THz region. In normal mode analysis of RTA we find a shearing motion that is shared by both the apo- and holo-RTAs, whereas a breathing motion, and an upward hinge rising and an alpha-G bending characteristic motion are dampened significantly upon AMP binding, suggesting these motions are involved in the necessary flexibility of the active site. In contrast, we find a normal mode motion that separates domains I and II of RTA at the interface that is more common in the holo-protein. We hypothesized that the flexibility of the entrance of RTA can facilitate the entry of rRNA and allow the substrate to adjust its conformation and orientation prior to depurination. This process suggests an rRNA binding pathway which is supplemental the current RTA depurination mechanism.