Deciphering the Path of <i>S-nitrosation</i> of Human Thioredoxin: Evidence of an Internal NO Transfer and Implication for the Cellular Responses to NO
Nitric oxide (NO) is a free radical with a signaling capacity. Its cellular functions are achieved mainly through <i>S-nitrosation</i> where thioredoxin (hTrx) is pivotal in the S-transnitrosation to specific cellular targets. In this study, we use NMR spectroscopy and mass spectrometry...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/7/1236 |
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| author | Vitor S. Almeida Lara L. Miller João P. G. Delia Augusto V. Magalhães Icaro P. Caruso Anwar Iqbal Fabio C. L. Almeida |
| author_facet | Vitor S. Almeida Lara L. Miller João P. G. Delia Augusto V. Magalhães Icaro P. Caruso Anwar Iqbal Fabio C. L. Almeida |
| author_sort | Vitor S. Almeida |
| collection | DOAJ |
| description | Nitric oxide (NO) is a free radical with a signaling capacity. Its cellular functions are achieved mainly through <i>S-nitrosation</i> where thioredoxin (hTrx) is pivotal in the S-transnitrosation to specific cellular targets. In this study, we use NMR spectroscopy and mass spectrometry to follow the mechanism of S-(trans)nitrosation of hTrx. We describe a site-specific path for <i>S-nitrosation</i> by measuring the reactivity of each of the 5 cysteines of hTrx using cysteine mutants. We showed the interdependence of the three cysteines in the nitrosative site. C73 is the most reactive and is responsible for all S-transnitrosation to other cellular targets. We observed NO internal transfers leading to C62 <i>S-nitrosation</i>, which serves as a storage site for NO. C69-SNO only forms under nitrosative stress, leading to hTrx nuclear translocation. |
| first_indexed | 2024-03-09T12:20:12Z |
| format | Article |
| id | doaj.art-cdeea946bcf5405092f7cf85110a3015 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T12:20:12Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-cdeea946bcf5405092f7cf85110a30152023-11-30T22:41:56ZengMDPI AGAntioxidants2076-39212022-06-01117123610.3390/antiox11071236Deciphering the Path of <i>S-nitrosation</i> of Human Thioredoxin: Evidence of an Internal NO Transfer and Implication for the Cellular Responses to NOVitor S. Almeida0Lara L. Miller1João P. G. Delia2Augusto V. Magalhães3Icaro P. Caruso4Anwar Iqbal5Fabio C. L. Almeida6Institute of Medical Biochemistry Leopoldo de Meis (IBqM), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-590, BrazilInstitute of Medical Biochemistry Leopoldo de Meis (IBqM), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-590, BrazilInstitute of Medical Biochemistry Leopoldo de Meis (IBqM), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-590, BrazilInstitute of Medical Biochemistry Leopoldo de Meis (IBqM), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-590, BrazilInstitute of Medical Biochemistry Leopoldo de Meis (IBqM), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-590, BrazilInstitute of Medical Biochemistry Leopoldo de Meis (IBqM), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-590, BrazilInstitute of Medical Biochemistry Leopoldo de Meis (IBqM), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-590, BrazilNitric oxide (NO) is a free radical with a signaling capacity. Its cellular functions are achieved mainly through <i>S-nitrosation</i> where thioredoxin (hTrx) is pivotal in the S-transnitrosation to specific cellular targets. In this study, we use NMR spectroscopy and mass spectrometry to follow the mechanism of S-(trans)nitrosation of hTrx. We describe a site-specific path for <i>S-nitrosation</i> by measuring the reactivity of each of the 5 cysteines of hTrx using cysteine mutants. We showed the interdependence of the three cysteines in the nitrosative site. C73 is the most reactive and is responsible for all S-transnitrosation to other cellular targets. We observed NO internal transfers leading to C62 <i>S-nitrosation</i>, which serves as a storage site for NO. C69-SNO only forms under nitrosative stress, leading to hTrx nuclear translocation.https://www.mdpi.com/2076-3921/11/7/1236<i>S-nitrosation</i>NMRthioredoxinpost-translational modificationmechanism of action |
| spellingShingle | Vitor S. Almeida Lara L. Miller João P. G. Delia Augusto V. Magalhães Icaro P. Caruso Anwar Iqbal Fabio C. L. Almeida Deciphering the Path of <i>S-nitrosation</i> of Human Thioredoxin: Evidence of an Internal NO Transfer and Implication for the Cellular Responses to NO Antioxidants <i>S-nitrosation</i> NMR thioredoxin post-translational modification mechanism of action |
| title | Deciphering the Path of <i>S-nitrosation</i> of Human Thioredoxin: Evidence of an Internal NO Transfer and Implication for the Cellular Responses to NO |
| title_full | Deciphering the Path of <i>S-nitrosation</i> of Human Thioredoxin: Evidence of an Internal NO Transfer and Implication for the Cellular Responses to NO |
| title_fullStr | Deciphering the Path of <i>S-nitrosation</i> of Human Thioredoxin: Evidence of an Internal NO Transfer and Implication for the Cellular Responses to NO |
| title_full_unstemmed | Deciphering the Path of <i>S-nitrosation</i> of Human Thioredoxin: Evidence of an Internal NO Transfer and Implication for the Cellular Responses to NO |
| title_short | Deciphering the Path of <i>S-nitrosation</i> of Human Thioredoxin: Evidence of an Internal NO Transfer and Implication for the Cellular Responses to NO |
| title_sort | deciphering the path of i s nitrosation i of human thioredoxin evidence of an internal no transfer and implication for the cellular responses to no |
| topic | <i>S-nitrosation</i> NMR thioredoxin post-translational modification mechanism of action |
| url | https://www.mdpi.com/2076-3921/11/7/1236 |
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