Atomic structure and enzymatic insights into the vancomycin-resistant Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit C
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 coun...
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| Format: | Journal Article |
| Language: | English |
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2020
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| Online Access: | https://hdl.handle.net/10356/142463 |
| _version_ | 1826124566118793216 |
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| author | Pan, Ankita Balakrishna, Asha Manikkoth Nartey, Wilson Kohlmeier, Andreas Dip, Phat Vinh Bhushan, Shashi Grüber, Gerhard |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Pan, Ankita Balakrishna, Asha Manikkoth Nartey, Wilson Kohlmeier, Andreas Dip, Phat Vinh Bhushan, Shashi Grüber, Gerhard |
| author_sort | Pan, Ankita |
| collection | NTU |
| description | 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 (2.8Å 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. |
| first_indexed | 2024-10-01T06:22:24Z |
| format | Journal Article |
| id | ntu-10356/142463 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:22:24Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1424632020-06-22T07:32:28Z Atomic structure and enzymatic insights into the vancomycin-resistant Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit C Pan, Ankita Balakrishna, Asha Manikkoth Nartey, Wilson Kohlmeier, Andreas Dip, Phat Vinh Bhushan, Shashi Grüber, Gerhard School of Biological Sciences NTU Institute of Structural Biology Science::Biological sciences Oxidative Stress Reactive Oxygen Species 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 (2.8Å 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. MOE (Min. of Education, S’pore) 2020-06-22T07:32:28Z 2020-06-22T07:32:28Z 2017 Journal Article Pan, A., Balakrishna, A. M., Nartey, W., Kohlmeier, A., Dip, P. V., Bhushan, S., & Grüber, G. (2018). Atomic structure and enzymatic insights into the vancomycin-resistant Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit C. Free Radical Biology and Medicine, 115, 252-265. doi:10.1016/j.freeradbiomed.2017.12.003 0891-5849 https://hdl.handle.net/10356/142463 10.1016/j.freeradbiomed.2017.12.003 29223533 2-s2.0-85037979045 115 252 265 en Free Radical Biology and Medicine © 2017 Elsevier Inc. All rights reserved. |
| spellingShingle | Science::Biological sciences Oxidative Stress Reactive Oxygen Species Pan, Ankita Balakrishna, Asha Manikkoth Nartey, Wilson Kohlmeier, Andreas Dip, Phat Vinh Bhushan, Shashi Grüber, Gerhard Atomic structure and enzymatic insights into the vancomycin-resistant Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit C |
| title | Atomic structure and enzymatic insights into the vancomycin-resistant Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit C |
| title_full | Atomic structure and enzymatic insights into the vancomycin-resistant Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit C |
| title_fullStr | Atomic structure and enzymatic insights into the vancomycin-resistant Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit C |
| title_full_unstemmed | Atomic structure and enzymatic insights into the vancomycin-resistant Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit C |
| title_short | Atomic structure and enzymatic insights into the vancomycin-resistant Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit C |
| title_sort | atomic structure and enzymatic insights into the vancomycin resistant enterococcus faecalis v583 alkylhydroperoxide reductase subunit c |
| topic | Science::Biological sciences Oxidative Stress Reactive Oxygen Species |
| url | https://hdl.handle.net/10356/142463 |
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