Atomic structure and enzymatic insights into the vancomycin-resistant Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit C

作者：Pan Ankita; Balakrishna Asha Manikkoth; Nartey Wilson; Kohlmeier Andreas; Dip Phat Vinh; Bhushan Shashi; Gruber Gerhard^*

来源：Free Radical Biology and Medicine, 2018, 115: 235-248.

DOI：10.1016/j.freeradbiomed.2017.12.003

• Oxidative stress
• Reactive oxygen species
• Peroxiredoxins
• Alkylhydroperoxide reductase
• AhpC
• Enterococcus faecalis

The Enterococcus faecalis alkyl hydroperoxide reductase complex (AhpR) with its subunits AhpC (EfAhpC) and AhpF (EfAhpF) are of paramount importance to restore redox homeostasis. Recently, the novel phenomenon of swapping of the catalytic domains of EfAhpF was uncovered. Here, we visualized its counterpart EfAhpC (187 residues) from the vancomycin-resistant E. faecalis (V583) bacterium by electron microscopy and demonstrate, that in contrast to other bacterial AhpCs, EfAhpC forms a stable decamer-ring irrespective of the redox state. The first crystallographic structure (2.8 angstrom resolution) of the C-terminal truncated form (EfAhpC1-172) confirms the decamer ring and provides new insight into a transition state in-between a fully folded to a locally unfolded conformation in the catalytic center due to redox modulation. Amino acid substitutions of residues in the N- and C-termini as well as the oligomeric interphase of EfAhpC provide information into their structural and enzymatic roles. Mutagenesis, enzymatic and biophysical studies reveal the effect of the unusual existence of four cysteines in EfAhpC, which might optimize the functional adaptation of the E. faecalis enzyme under various physiological conditions.

• 出版日期2018-2-1
• 单位南阳理工学院; MIT