Glutaredoxin catalysis requires two distinct glutathione interaction sites
Glutaredoxins are key players in cellular redox homoeostasis and exert a variety of essential functions ranging from glutathione-dependent catalysis to iron metabolism. The exact structure-function relationships and mechanistic differences among glutaredoxins that are active or inactive in standard...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
04 April 2017
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| In: |
Nature Communications
Year: 2017, Volume: 8 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms14835 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1038/ncomms14835 Verlag, kostenfrei, Volltext: https://www.nature.com/articles/ncomms14835 
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| Author Notes: | Patricia Begas, Linda Liedgens, Anna Moseler, Andreas J. Meyer & Marcel Deponte |
| Summary: | Glutaredoxins are key players in cellular redox homoeostasis and exert a variety of essential functions ranging from glutathione-dependent catalysis to iron metabolism. The exact structure-function relationships and mechanistic differences among glutaredoxins that are active or inactive in standard enzyme assays have so far remained elusive despite numerous kinetic and structural studies. Here, we elucidate the enzymatic mechanism showing that glutaredoxins require two distinct glutathione interaction sites for efficient redox catalysis. The first site interacts with the glutathione moiety of glutathionylated disulfide substrates. The second site activates glutathione as the reducing agent. We propose that the requirement of two distinct glutathione interaction sites for the efficient reduction of glutathionylated disulfide substrates explains the deviating structure-function relationships, activities and substrate preferences of different glutaredoxin subfamilies as well as thioredoxins. Our model also provides crucial insights for the design or optimization of artificial glutaredoxins, transition-state inhibitors and glutaredoxin-coupled redox sensors. |
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| Item Description: | Gesehen am 12.10.2018 |
| Physical Description: | Online Resource |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms14835 |