Journal article
ddhCTP produced by the radical‐SAM activity of RSAD2 (viperin) inhibits the NAD+‐dependent activity of enzymes to modulate metabolism
- Abstract:
- Radical S‐adenosylmethionine (SAM) domain‐containing protein 2 (RSAD2; viperin) is a key enzyme in innate immune responses that is highly expressed in response to viral infection and inflammatory stimuli in many cell types. Recently, it was found that RSAD2 catalyses transformation of cytidine triphosphate (CTP) to its analogue 3´‐deoxy‐3´,4´‐didehydro‐CTP (ddhCTP). The cellular function of this metabolite is unknown. Here, we analysed the extra‐ and intracellular metabolite levels in induced pluripotent stem cell (iPSC)‐derived macrophages using high resolution LC‐MS/MS. The results together with biochemical assays and molecular docking simulations revealed that ddhCTP inhibits the NAD+‐dependent activity of enzymes including that of the house‐keeping enzyme glyceraldehyde 3‐phosphate dehydrogenase (GAPDH). We propose that ddhCTP regulates cellular metabolism in response to inflammatory stimuli such as viral infection, pointing to a broader function of RSAD2 than previously thought.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Accepted manuscript, 678.5KB, Terms of use)
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- Publisher copy:
- 10.1002/1873-3468.13778
Authors
- Publisher:
- Wiley
- Journal:
- FEBS Letters More from this journal
- Publication date:
- 2020-03-30
- Acceptance date:
- 2020-03-16
- DOI:
- EISSN:
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1873-3468
- ISSN:
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0014-5793
- Language:
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English
- Keywords:
- Pubs id:
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1097728
- Local pid:
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pubs:1097728
- Deposit date:
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2020-03-31
Terms of use
- Copyright holder:
- Kourosh Honarmand Ebrahimi et al.
- Copyright date:
- 2020
- Rights statement:
- Copyright © 2020 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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