Figure 6.

Non-covalent stabilization of the FF conformation can promote hyperoxidation. A. Protein surface area buried by crystal contacts (gray) has substantial overlap with magnitudes of conformation change (red) on a per residue basis along the chain. The C_P (Cys48) and C_R (Cys84) positions are denoted (*). Residues 79–81, not well defined in the LU structure, were assigned a shift of 10 Å based on their neighbors. B. One crystal contact region in the FF XcPrxQ crystals (white for main molecule and gray for symmetry mate) overlaid with LU structure (black) shows FF→LU movement (brown arrows) of Phe83 is prevented by a steric clash with Arg103 of the symmetry mate (red) because the two side chains would be 1.3 Å apart. C. A general mechanism for Prx catalysis and hyperoxidation is shown, as has been previously proposed (Sevilla et al., 2015)(Perkins et al., 2015)(Perkins et al., 2014), that highlights the key physiologically-relevant redox states that have been captured at atomic resolution for XcPrxQ. Also emphasized is that inhibiting facile unfolding enhances inactivation. This has been observed to occur for sensitive Prx1-subfamily members by stabilization by the C-terminal tail (Wood et al., 2003). In the case of XcPrxQ, the FF crystal form can be conceptually considered as a large non-covalent FF-conformation-stabilizing inhibitor, trapping the enzyme as FF and promoting inactivation.