Direct Observation of Methylmercury and Auranofin Binding to Selenocysteine in Thioredoxin Reductase
(2020) In Inorganic Chemistry 59(5). p.2711-2718- Abstract
Selenoenzymes, containing a selenocysteine (Sec) residue, fulfill important roles in biology. The mammalian thioredoxin reductase selenoenzymes are key regulators of antioxidant defense and redox signaling and are inhibited by methylmercury species and by the gold-containing drug auranofin. It has been proposed that such inhibition is mediated by metal binding to Sec in the enzyme. However, direct structural observations of these classes of inhibitors binding to selenoenzymes have been few to date. Here we therefore have used extended X-ray absorption fine structure as a direct structural probe to investigate binding to the selenium site in recombinant rat thioredoxin reductase 1 (TrxR1). The results demonstrate for the first time the... (More)
Selenoenzymes, containing a selenocysteine (Sec) residue, fulfill important roles in biology. The mammalian thioredoxin reductase selenoenzymes are key regulators of antioxidant defense and redox signaling and are inhibited by methylmercury species and by the gold-containing drug auranofin. It has been proposed that such inhibition is mediated by metal binding to Sec in the enzyme. However, direct structural observations of these classes of inhibitors binding to selenoenzymes have been few to date. Here we therefore have used extended X-ray absorption fine structure as a direct structural probe to investigate binding to the selenium site in recombinant rat thioredoxin reductase 1 (TrxR1). The results demonstrate for the first time the direct and complete binding of the metal atom of the inhibitors to the selenium atom in TrxR1 for both methylmercury and auranofin, indicating that TrxR1 inhibition indeed can be attributed to such direct metal-selenium binding.
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- author
- Pickering, Ingrid J. ; Cheng, Qing ; Rengifo, Emérita Mendoza ; Nehzati, Susan LU ; Dolgova, Natalia V. ; Kroll, Thomas ; Sokaras, Dimosthenis ; George, Graham N. and Arnér, Elias S.J.
- publishing date
- 2020-03-02
- type
- Contribution to journal
- publication status
- published
- in
- Inorganic Chemistry
- volume
- 59
- issue
- 5
- pages
- 8 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:32049511
- scopus:85079769004
- ISSN
- 0020-1669
- DOI
- 10.1021/acs.inorgchem.9b03072
- language
- English
- LU publication?
- no
- id
- bf962e7b-099f-47e6-956a-f9e2760b3d6f
- date added to LUP
- 2020-09-05 20:25:14
- date last changed
- 2024-06-12 20:01:51
@article{bf962e7b-099f-47e6-956a-f9e2760b3d6f,
abstract = {{<p>Selenoenzymes, containing a selenocysteine (Sec) residue, fulfill important roles in biology. The mammalian thioredoxin reductase selenoenzymes are key regulators of antioxidant defense and redox signaling and are inhibited by methylmercury species and by the gold-containing drug auranofin. It has been proposed that such inhibition is mediated by metal binding to Sec in the enzyme. However, direct structural observations of these classes of inhibitors binding to selenoenzymes have been few to date. Here we therefore have used extended X-ray absorption fine structure as a direct structural probe to investigate binding to the selenium site in recombinant rat thioredoxin reductase 1 (TrxR1). The results demonstrate for the first time the direct and complete binding of the metal atom of the inhibitors to the selenium atom in TrxR1 for both methylmercury and auranofin, indicating that TrxR1 inhibition indeed can be attributed to such direct metal-selenium binding.</p>}},
author = {{Pickering, Ingrid J. and Cheng, Qing and Rengifo, Emérita Mendoza and Nehzati, Susan and Dolgova, Natalia V. and Kroll, Thomas and Sokaras, Dimosthenis and George, Graham N. and Arnér, Elias S.J.}},
issn = {{0020-1669}},
language = {{eng}},
month = {{03}},
number = {{5}},
pages = {{2711--2718}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Inorganic Chemistry}},
title = {{Direct Observation of Methylmercury and Auranofin Binding to Selenocysteine in Thioredoxin Reductase}},
url = {{http://dx.doi.org/10.1021/acs.inorgchem.9b03072}},
doi = {{10.1021/acs.inorgchem.9b03072}},
volume = {{59}},
year = {{2020}},
}