A theoretical framework for the development of dynamic nuclear polarization neutron macromolecular crystallography to advance the resolution of H atoms within biomolecular crystals is presented #DynamicNuclearPolarization #PhaseRetrieval #Hydrogen doi.org/10.1107/S205...

Monooxygenase Activity of Indoleamine 2,3-Dioxygenase Indoleamine 2,3-dioxygenase (IDO) is a heme-dependent enzyme that catalyzes the first, rate-limiting step of the kynurenine pathway─the oxidation of l-tryptophan to N-formylkynurenine (NFK). IDO-catalyzed depletion of tryptophan levels and accumulation of kynurenine pathway metabolites is an important control mechanism of the immune responses in cells. IDO has been considered as a dioxygenase because two atoms of oxygen are inserted into the substrate. Here, we use LC-MS and NMR to examine the reactivity of human IDO (hIDO) with l-tryptophan (l-Trp) and several other tryptophan analogues. Alongside dioxygenase activity, we identify a concurrent pathway of heme-dependent monooxygenase activity in the reaction of hIDO with l-Trp, leading to the formation of a cyclic 3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid (HPIC) species. Reaction profiles for the reaction of hIDO with other tryptophan analogues are likewise examined. Formation of HPIC from l-Trp is reproduced in HeLa cells induced to overexpress hIDO, indicating that this dual dioxygenase/monooxygenase reactivity also occurs biologically. Notably, the reaction of hIDO with β-[3-benzo(b)thienyl]-l-alanine (S-l-Trp)─a known inhibitor ─yielded only the cyclic HPIC analogue, suggesting that IDO activity can be selectively directed toward the monooxygenase pathway. Molecular dynamics simulations underscore the critical role of substrate plasticity within the active site of hIDO, while DFT calculations provide a mechanistic rationalization for the observed product distributions. Together, the data demonstrate dual dioxygenase/monooxygenase functionality for human IDO. As the overall gatekeeper for control of tryptophan levels in cells, the findings provide mechanistic information on relevance to therapeutic strategies focused on IDO inhibition.

Absolutely delighted to have been included in this new twist to the story. Monooxygenase Activity of Indoleamine 2,3-Dioxygenase | Journal of the American Chemical Society pubs.acs.org/doi/10.1021/...

Looking to start your lab in generative biology / AI?
Come join us at the @sangerinstitute.bsky.social
Sanger is core-funded so you can generate data at scale to train the next generation of models and understanding. Design/Engineering/Chemistry/Proteins/Pathways!
pls RT
tinyurl.com/GenGenFaculty

Samples vary. Comment added

"whizzing electrons" - From BBC News

Outside Back Cover: Solvent Channels and Electric Fields Guide Proton Delivery to the Active Site of Heme Peroxidases Local electric fields guide protons toward the heme through two distinct electrostatic funnels at the γ- and δ-edges in heme peroxidases. Water-mediated pathways enable proton exchange with key resid...

doi.org/10.1002/ange... absolutely delighted to have been included in this.
@leicstructbio.bsky.social

The Great AI Bubble Yes, it's a bubble. And yes, it's going to burst.

As noted by Dave the Bragg broligarchy.substack.com/p/the-great-...

(BBSRC NWD) A novel redox mechanosignalling nexus in the synapse that is misregulated in neurodegeneration at University of Liverpool on FindAPhD.com PhD Project - (BBSRC NWD) A novel redox mechanosignalling nexus in the synapse that is misregulated in neurodegeneration at University of Liverpool, listed on FindAPhD.com

🧠 Fully funded 4-year PhD studentship 🧠 Please repost

BBSRC NWD project with @parikki.bsky.social and @iamabyron.bsky.social

Come join us to look at how mechanical and oxidative stress signalling pathways converge on the synaptic scaffold protein talin.

www.findaphd.com/phds/project...

Dr Emma Hesketh @heskethemma.bsky.social tells us about what we can do with the Midlands Regional CryoEM facility

Spread the word if you can.
We have an unused stopped flow accessory from Applied Photophysics. We traded in our Chirascan CD instrument so we have no use for this anymore. Reach out if you are interested and can find a home for this setup. Will ofcourse only work with a Chirascan!

💠 The ACA community mourns the loss of Dr. Benno P. Schoenborn (1938–2025), a pioneer in neutron protein crystallography whose work transformed structural biology.
Read more and share memories: 🔗 bit.ly/42wNvlM
#crystallography #InMemoriam #ACACommunity #neutrondiffraction

Defend Press Freedom I stand with Declassified UK - I've just signed my name. Join me in telling Westminster that you care about freedom of the press.

✒️ Parliament has been accused of an “outrageous abuse” that is “worthy of the Trump White House”, after refusing to issue us a media pass.

Thousands have signed a petition calling on the government to give us access.

Help defend press freedom, sign today.

secure.declassifieduk.org/page/178447/...

Solvent Channels and Electric Fields Guide Proton Delivery to the Active Site of Heme Peroxidases Electrostatic potential surfaces and electric field lines reveal that local fields guide proton delivery through multiple conserved solvent channels in heme peroxidases, enabling efficient access to ....

How do protons get delivered to the active site of heme peroxidases? A combination of solvent channels and electric fields, say @petermoody.bsky.social
onlinelibrary.wiley.com/doi/10.1002/...

Show Your Stripes Visualising how the climate has changed for every country across the globe

showyourstripes.info/c/europe/uni...

Leicester Temperature 1850-2024 showyourstripes.info/s/europe/uni...

A geological timescale for bacterial evolution and oxygen adaptation Microbial life has dominated Earth’s history but left a sparse fossil record, greatly hindering our understanding of evolution in deep time. However, bacterial metabolism has left signatures in the ge...

Ecstatic to have played a small part in this, we find that the first aerobes predate the GOE by almost a billion years! Photosynthesis implications

Lead by Adrián Davín, @benjwoodcroft.bsky.social @xrefugee13.bsky.social @tweethinking.bsky.social @ssolo.bsky.social

www.science.org/doi/10.1126/...

Can AlphaFold refine structures for X-ray & Cryo-EM/ET data? Now it can! Great collab with @moalquraishi.bsky.social and @randyjread.bsky.social led by @alisiafadini.bsky.social and @minhuanli.bsky.social. 🧵below. Code to follow...

George Sheldrick will be missed🕯️🕯️🕯️#SHELX #crystallography #education

Well over 600 signatories now. Please keep the momentum going.

Sign and share to show how much the wider scientific community is concerned by the Royal Society's silence over Musk's FRS.

Members of the UK and international scientific community are all welcome to sign.

Really cool project to work on, happy to see it out!

Evaluating the impact of chemically reactive metabolites in premature ageing at University of Leicester on FindAPhD.com PhD Project - Evaluating the impact of chemically reactive metabolites in premature ageing at University of Leicester, listed on FindAPhD.com

**ALERT**

Just a couple of days left to apply for this PhD opportunity in the Hopkinson and Tanaka groups in Leicester.

Evaluating the impact of chemically reactive metabolites in premature ageing

BBSRC MIBTP studentship - 4 years fully funded

www.findaphd.com/phds/project...

Picture of crystals viewed with polarised light. Photo credit Christopher Hutchinson

Crystals on front cover of Imperial alumni mag! 👍Shame the story it links to is narcissistic self-congratatory bollocks

2024's Biggest Breakthroughs in Biology and Neuroscience YouTube video by Quanta Magazine

Wow! A real honour to be included on this year's list, thanks @quantamagazine.bsky.social and of course all the vital collaborators involved in the work youtu.be/p9XHI_26cPE?...

Thank you to all the contributors

Front cover of Methods in Enzymology vol 709 edited by Hanna Kwon & Peter Moody

Better picture!

Thank you everyone who contributed, I will post a list later.

@leicstructbio.bsky.social

Electron diffraction from protein crystal

Electron diffraction! From the awesome Hanna Kwon and Marcus Gallagher-Jones

Great to see it out! Paper itself wouldn't be possible, of course, without a veritable horde of collaborators, and thanks very much for @jonlambert.bsky.social for writing such a wonderful commentary!