Residues of helix ɑ2 are critical for catalytic efficiency of mycobacterial alkylhydroperoxide reductase subunit C
The ability of Mycobacteria to overcome oxidative stress is of paramount importance for its survival within the host. One of the key enzymes that are involved in protecting the bacterium from reactive oxygen species is the catalase-peroxidase (KatG). However, in strains resistant to the antibiotic i...
| Main Authors: | , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2021
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| Online Access: | https://hdl.handle.net/10356/154287 |
| _version_ | 1811694831382036480 |
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| author | Chong, Shi Min Sherilyn Kamariah, Neelagandan Grüber, Gerhard |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Chong, Shi Min Sherilyn Kamariah, Neelagandan Grüber, Gerhard |
| author_sort | Chong, Shi Min Sherilyn |
| collection | NTU |
| description | The ability of Mycobacteria to overcome oxidative stress is of paramount importance for its survival within the host. One of the key enzymes that are involved in protecting the bacterium from reactive oxygen species is the catalase-peroxidase (KatG). However, in strains resistant to the antibiotic isoniazid, KatG is rendered ineffective, which is associated with an increased expression of alkylhydroperoxide reductase subunit C (AhpC). Mycobacterial AhpC possesses a unique helical displacement when compared to its bacterial counterparts. Here, via mutagenesis studies, we demonstrate the importance of this helix for redox modulation of the catalytic activity of AhpC. Along with structural insights from crystallographic data, the impact of critical residues on the structure and flexibility of the helix and on AhpC oligomerization is described. |
| first_indexed | 2024-10-01T07:13:49Z |
| format | Journal Article |
| id | ntu-10356/154287 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:13:49Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1542872021-12-16T08:25:46Z Residues of helix ɑ2 are critical for catalytic efficiency of mycobacterial alkylhydroperoxide reductase subunit C Chong, Shi Min Sherilyn Kamariah, Neelagandan Grüber, Gerhard School of Biological Sciences School of Physical and Mathematical Sciences Interdisciplinary Graduate School (IGS) Nanyang Institute of Technology in Health and Medicine Science::Biological sciences Alkylhydroperoxide Reductase Mycobacteria The ability of Mycobacteria to overcome oxidative stress is of paramount importance for its survival within the host. One of the key enzymes that are involved in protecting the bacterium from reactive oxygen species is the catalase-peroxidase (KatG). However, in strains resistant to the antibiotic isoniazid, KatG is rendered ineffective, which is associated with an increased expression of alkylhydroperoxide reductase subunit C (AhpC). Mycobacterial AhpC possesses a unique helical displacement when compared to its bacterial counterparts. Here, via mutagenesis studies, we demonstrate the importance of this helix for redox modulation of the catalytic activity of AhpC. Along with structural insights from crystallographic data, the impact of critical residues on the structure and flexibility of the helix and on AhpC oligomerization is described. Ministry of Education (MOE) Nanyang Technological University This study was supported by the AcademicResearch Fund (AcRF) Tier 1 ID889 Ministry of Edu-cation, Singapore, to GG, SMSC is grateful to receivean NTU Research Scholarship at Nanyang Technolog-ical University, Singapore. 2021-12-16T08:25:45Z 2021-12-16T08:25:45Z 2020 Journal Article Chong, S. M. S., Kamariah, N. & Grüber, G. (2020). Residues of helix ɑ2 are critical for catalytic efficiency of mycobacterial alkylhydroperoxide reductase subunit C. FEBS Letters, 594(17), 2829-2839. https://dx.doi.org/10.1002/1873-3468.13864 0014-5793 https://hdl.handle.net/10356/154287 10.1002/1873-3468.13864 32557576 2-s2.0-85088089382 17 594 2829 2839 en ID889 FEBS Letters © 2020 Federation of European Biochemical Societies. All rights reserved. |
| spellingShingle | Science::Biological sciences Alkylhydroperoxide Reductase Mycobacteria Chong, Shi Min Sherilyn Kamariah, Neelagandan Grüber, Gerhard Residues of helix ɑ2 are critical for catalytic efficiency of mycobacterial alkylhydroperoxide reductase subunit C |
| title | Residues of helix ɑ2 are critical for catalytic efficiency of mycobacterial alkylhydroperoxide reductase subunit C |
| title_full | Residues of helix ɑ2 are critical for catalytic efficiency of mycobacterial alkylhydroperoxide reductase subunit C |
| title_fullStr | Residues of helix ɑ2 are critical for catalytic efficiency of mycobacterial alkylhydroperoxide reductase subunit C |
| title_full_unstemmed | Residues of helix ɑ2 are critical for catalytic efficiency of mycobacterial alkylhydroperoxide reductase subunit C |
| title_short | Residues of helix ɑ2 are critical for catalytic efficiency of mycobacterial alkylhydroperoxide reductase subunit C |
| title_sort | residues of helix ɑ2 are critical for catalytic efficiency of mycobacterial alkylhydroperoxide reductase subunit c |
| topic | Science::Biological sciences Alkylhydroperoxide Reductase Mycobacteria |
| url | https://hdl.handle.net/10356/154287 |
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