Molecular dynamics simulation approach to explore atomistic molecular mechanism of peroxidase activity of apoptotic cytochrome c mutants
Mutations in cytochrome c (Cyt c) have been reported in tuning peroxidase activity, which in-turn cause Cyt c release from mitochondria and early apoptosis. However, the molecular tuning mechanism underlying this activity remains elusive. Herein, multiple 20 ns molecular dynamics (MD) simulations of...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-01-01
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| Series: | Informatics in Medicine Unlocked |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352914818300613 |
| _version_ | 1811299314689900544 |
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| author | Gurusamy Muneeswaran Manickam Pandiaraj Subramanian Kartheeswaran Muniyandi Sankaralingam Kaliappan Muthukumar Chandran Karunakaran |
| author_facet | Gurusamy Muneeswaran Manickam Pandiaraj Subramanian Kartheeswaran Muniyandi Sankaralingam Kaliappan Muthukumar Chandran Karunakaran |
| author_sort | Gurusamy Muneeswaran |
| collection | DOAJ |
| description | Mutations in cytochrome c (Cyt c) have been reported in tuning peroxidase activity, which in-turn cause Cyt c release from mitochondria and early apoptosis. However, the molecular tuning mechanism underlying this activity remains elusive. Herein, multiple 20 ns molecular dynamics (MD) simulations of wild type (WT), Y67F and K72W mutated Cyt c in aqueous solutions have been carried out to study how the changes in structural features alters the peroxidase activity of the protein. MD simulation results indicate that Y67F mutation caused, (i) increased distances between critical electron-transfer residues, (ii) higher fluctuations in omega loops, and (iii) weakening of intraprotein hydrogen bonds result in open conformation at heme crevice loop in Cyt c leading to an enhanced peroxidase activity. Interestingly, the aforementioned structural features are strengthened in K72W compared to WT and Y67F, which triggers K72W mutated Cyt c into a poor peroxidase. Essential dynamics results unveil that first two eigenvectors are responsible for overall motions of WT, Y67F and K72W mutated Cyt c. This study thus provides atomic level insight into molecular mechanism of peroxidase activity of Cyt c, which will help in designing novel Cyt c structures that is more desirable than natural Cyt c for biomedical and industrial processes. Keywords: Peroxidase activity, Cytochrome c, Mutations, Apoptosis, Molecular dynamics |
| first_indexed | 2024-04-13T06:33:24Z |
| format | Article |
| id | doaj.art-fc6641b5507c446e9ea0f6f2c72957fb |
| institution | Directory Open Access Journal |
| issn | 2352-9148 |
| language | English |
| last_indexed | 2024-04-13T06:33:24Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Informatics in Medicine Unlocked |
| spelling | doaj.art-fc6641b5507c446e9ea0f6f2c72957fb2022-12-22T02:58:02ZengElsevierInformatics in Medicine Unlocked2352-91482018-01-01115160Molecular dynamics simulation approach to explore atomistic molecular mechanism of peroxidase activity of apoptotic cytochrome c mutantsGurusamy Muneeswaran0Manickam Pandiaraj1Subramanian Kartheeswaran2Muniyandi Sankaralingam3Kaliappan Muthukumar4Chandran Karunakaran5Biomedical Research Lab, Department of Chemistry, VHNSN College (Autonomous), Virudhunagar, Tamilnadu, India; Department of Chemistry, School of Advanced Sciences, Kalasalingam Academy of Research and Education, Krishnankoil, 626 126, Tamilnadu, India; Corresponding author. Department of Chemistry, School of Advanced Sciences, Kalasalingam Academy of Research and Education, Krishnanakoil, 626 126, Tamilnadu, India.Electrodics and Electrocatalysis Division, CSIR-Central Electrochemical Research Institute, Karaikudi, 630003, IndiaDepartment of Master of Computer Applications, School of Computing, Kalasalingam Academy of Research and Education, Krishnankoil, 626 126, Tamilnadu, IndiaDepartment of Chemistry and Nano Science, Ewha Womans University, Seoul, 03760, South KoreaApplied Materials, Sunnyvale, 94085, CA, USABiomedical Research Lab, Department of Chemistry, VHNSN College (Autonomous), Virudhunagar, Tamilnadu, India; Corresponding author.Mutations in cytochrome c (Cyt c) have been reported in tuning peroxidase activity, which in-turn cause Cyt c release from mitochondria and early apoptosis. However, the molecular tuning mechanism underlying this activity remains elusive. Herein, multiple 20 ns molecular dynamics (MD) simulations of wild type (WT), Y67F and K72W mutated Cyt c in aqueous solutions have been carried out to study how the changes in structural features alters the peroxidase activity of the protein. MD simulation results indicate that Y67F mutation caused, (i) increased distances between critical electron-transfer residues, (ii) higher fluctuations in omega loops, and (iii) weakening of intraprotein hydrogen bonds result in open conformation at heme crevice loop in Cyt c leading to an enhanced peroxidase activity. Interestingly, the aforementioned structural features are strengthened in K72W compared to WT and Y67F, which triggers K72W mutated Cyt c into a poor peroxidase. Essential dynamics results unveil that first two eigenvectors are responsible for overall motions of WT, Y67F and K72W mutated Cyt c. This study thus provides atomic level insight into molecular mechanism of peroxidase activity of Cyt c, which will help in designing novel Cyt c structures that is more desirable than natural Cyt c for biomedical and industrial processes. Keywords: Peroxidase activity, Cytochrome c, Mutations, Apoptosis, Molecular dynamicshttp://www.sciencedirect.com/science/article/pii/S2352914818300613 |
| spellingShingle | Gurusamy Muneeswaran Manickam Pandiaraj Subramanian Kartheeswaran Muniyandi Sankaralingam Kaliappan Muthukumar Chandran Karunakaran Molecular dynamics simulation approach to explore atomistic molecular mechanism of peroxidase activity of apoptotic cytochrome c mutants Informatics in Medicine Unlocked |
| title | Molecular dynamics simulation approach to explore atomistic molecular mechanism of peroxidase activity of apoptotic cytochrome c mutants |
| title_full | Molecular dynamics simulation approach to explore atomistic molecular mechanism of peroxidase activity of apoptotic cytochrome c mutants |
| title_fullStr | Molecular dynamics simulation approach to explore atomistic molecular mechanism of peroxidase activity of apoptotic cytochrome c mutants |
| title_full_unstemmed | Molecular dynamics simulation approach to explore atomistic molecular mechanism of peroxidase activity of apoptotic cytochrome c mutants |
| title_short | Molecular dynamics simulation approach to explore atomistic molecular mechanism of peroxidase activity of apoptotic cytochrome c mutants |
| title_sort | molecular dynamics simulation approach to explore atomistic molecular mechanism of peroxidase activity of apoptotic cytochrome c mutants |
| url | http://www.sciencedirect.com/science/article/pii/S2352914818300613 |
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