ChemBioHub - Huber Lab
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chembiohub.bsky.social
ChemBioHub - Huber Lab
@chembiohub.bsky.social
We are a chemical biology lab at the Nuffield Department of Medicine at the University of Oxford.
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New in @science.org 🧬

What if an enzyme you thought you knew turned out to control metabolism in a completely new way?

We found that NUDT5 acts as a molecular handbrake on purine synthesis, reshaping how cells make DNA building blocks and respond to cancer drugs.

www.science.org/doi/10.1126/...
A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis
Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. By investigating chemical and genetic depende...
www.science.org
Congratulations @jourdainlab.bsky.social !
November 13, 2025 at 2:15 PM
Thank you for sharing! We’re lucky to have support from @ihieurope.bsky.social and @horizoneu.bsky.social - it’s the kind of open, collaborative funding that lets discoveries like this happen here in Oxford (and beyond!).
November 7, 2025 at 9:51 AM
Thank you so much, @rjdlab.bsky.social! Great to see our independent studies complement each other so beautifully and deepen the picture of purine metabolism.
November 6, 2025 at 8:40 PM
Reposted by ChemBioHub - Huber Lab
Here's the beautiful paper from @chembiohub.bsky.social reporting NUDT5's role in purine synthesis. I cannot emphasize enough how gracious and open these authors were when we all realized we were working on the same mechanism.
New in @science.org 🧬

What if an enzyme you thought you knew turned out to control metabolism in a completely new way?

We found that NUDT5 acts as a molecular handbrake on purine synthesis, reshaping how cells make DNA building blocks and respond to cancer drugs.

www.science.org/doi/10.1126/...
A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis
Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. By investigating chemical and genetic depende...
www.science.org
November 6, 2025 at 8:33 PM
Thank you - much appreciated!
November 6, 2025 at 8:26 PM
Reposted by ChemBioHub - Huber Lab
Beautiful discovery by the Huber and Kubicek labs and a wonderful example of using targeted protein degradation to probe novel non-catalytic functions.
New in @science.org 🧬

What if an enzyme you thought you knew turned out to control metabolism in a completely new way?

We found that NUDT5 acts as a molecular handbrake on purine synthesis, reshaping how cells make DNA building blocks and respond to cancer drugs.

www.science.org/doi/10.1126/...
A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis
Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. By investigating chemical and genetic depende...
www.science.org
November 6, 2025 at 8:12 PM
Thanks Jordan!
November 6, 2025 at 8:24 PM
Reposted by ChemBioHub - Huber Lab
1/New paper from Zheng Wu, Phong Nguyen et al. @cri-utsw.bsky.social shows how cells balance the two pathways that produce purine nucleotides: de novo purine biosynthesis (DNPB) and purine salvage. The surprising mechanism involves NUDT5, a Nudix hydrolase

www.science.org/doi/10.1126/...
NUDT5 regulates purine metabolism and thiopurine sensitivity by interacting with PPAT
Cells generate purine nucleotides through de novo purine biosynthesis (DNPB) and purine salvage. Purine salvage represses DNPB to prevent excessive purine nucleotide synthesis through mechanisms that ...
www.science.org
November 6, 2025 at 7:01 PM
Reposted by ChemBioHub - Huber Lab
17/NUDT5 is having a moment – see excellent work from other labs reporting roles for NUDT5 in purine metabolism. These include papers by Kilian Huber and Stefan Kubicek, also out today (see link), and work by Alexis Jourdain and Jun Yang (see next posts)
www.science.org/doi/10.1126/...
A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis
Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. By investigating chemical and genetic depende...
www.science.org
November 6, 2025 at 7:10 PM
JCI study underscores the role of NUDT5 in shaping patient response to thiopurines, pointing to opportunities for more individualised treatment.

www.jci.org/articles/vie...
JCI - The NUDIX hydrolase NUDT5 regulates thiopurine metabolism and cytotoxicity
www.jci.org
November 6, 2025 at 7:41 PM
Grateful to Stefan Kubicek & team @cemm.oeaw.ac.at for a fantastic collaboration. Big thanks also to
@ox.ac.uk
@ndm.ox.ac.uk
@cmd.ox.ac.uk
and funders
@horizoneu.bsky.social
@wellcometrust.bsky.social
November 6, 2025 at 7:39 PM
🌍 Why it matters: This changes how we think about enzyme regulation, metabolism, and cancer-drug response - and shows the power of chemistry to reveal new biology.
November 6, 2025 at 7:34 PM
🔬 Using proteomics, we discovered NUDT5 binds PPAT, the rate-limiting enzyme in de novo purine synthesis - a “handbrake” mechanism linking metabolism and disease.
November 6, 2025 at 7:33 PM
🧪 What we did: Tested NUDT5 enzyme inhibitors (no effect) → built a selective NUDT5 degrader (dNUDT5).
Removing the protein revealed an entirely non-enzymatic scaffolding function. #gottaloveTPD
November 6, 2025 at 7:33 PM
🧩 Motivation: In a CRISPR screen in a “folate trap” model, NUDT5 emerged as a rescue factor in MTHFD1-deficient cells - hinting at a deeper role in cellular metabolism.
November 6, 2025 at 7:32 PM
New in @science.org 🧬

What if an enzyme you thought you knew turned out to control metabolism in a completely new way?

We found that NUDT5 acts as a molecular handbrake on purine synthesis, reshaping how cells make DNA building blocks and respond to cancer drugs.

www.science.org/doi/10.1126/...
A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis
Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. By investigating chemical and genetic depende...
www.science.org
November 6, 2025 at 7:30 PM
Reposted by ChemBioHub - Huber Lab
If you have defended your PhD in Biochemistry or a related field in 2023 or have a publication in this field in 2023 (PhD less than 4 years ago), consider applying for the Förderpreis of the @gdchbiochem.bsky.social of @gdch.bsky.social.

Deadline: April 30th.

en.gdch.de/network-stru...
Awards & Honors | Gesellschaft Deutscher Chemiker e.V.
en.gdch.de
April 15, 2024 at 12:25 PM
Reposted by ChemBioHub - Huber Lab
Jensen Huang’s comments from JPM24 are now summarized in a Nvidia blog post. He doubles down on exactly the kinds of things that I’ve been cautioning are wildly optimistic. More below. 👇🏽 1/
January 18, 2024 at 12:09 PM
We have two postdoc positions available for structural biologists to help us study the function of proteins involved in RNA & ubiquitin metabolism. Deadline 9th October 2023. Links: 1) tinyurl.com/msc4vckb 2) tinyurl.com/4dukkuy6
October 5, 2023 at 12:48 PM
Excited to inaugurate our Bluesky account with this paper from our friends in the Tan lab on a matrix-augmented pooling strategy for thermal profiling - glad we could contribute! www.sciencedirect.com/science/arti...
Target deconvolution with matrix-augmented pooling strategy reveals cell-specific drug-protein inter...
Target deconvolution is a crucial but costly and time-consuming task that hinders large-scale profiling for drug discovery. We present a matrix-augmen…
www.sciencedirect.com
August 31, 2023 at 4:37 PM
Hello Bluesky! Please tell us why you had to hide away for sooo long!
August 31, 2023 at 4:31 PM