New lab preprint!
@zestytoast.bsky.social tagged a scarce mycobacterial protein in M. smegmatis with TwinStep but got… something? @kjamali.bsky.social's ModelAngelo built models & @martinsteinegger.bsky.social's FoldSeek IDed them as the biotin-containing MCC & LCC complexes
🧵
tinyurl.com/ukny4ptz

EtfD links beta oxidation to OxPhos in mycobacteria - recent work suggests that targeting EtfD could shorten #tubeculosis treatment.
But how does EtfD work? And how can you assay its activity?
In his final PhD manuscript @courbongautier.bsky.social provides answers!
www.biorxiv.org/content/10.1...

Now published J. Med. Chem! @zestytoast.bsky.social's structure of type II NADH dehydrogenase from mycobacteria. A promising drug target for TB & other mycobacterial infections, Yingke demonstrates how an inhibitor can block transfer of electrons from NADH to the ETC.
pubs.acs.org/doi/full/10....

Most protein complexes are born only once. V-ATPase assembles over and over as part of its regulatory mechanism, enabled by RAVE (regulator of ATPase of vacuoles and endosomes)
@hanlinw222.bsky.social's 1st struct of RAVE bound to a partial V1 complex now out in PNAS.
www.pnas.org/doi/10.1073/...

With his new book 'Everything Is Tuberculosis,' author @johngreensbluesky.bsky.social is breathing new life into tuberculosis advocacy

www.forbes.com/sites/madhuk...

In @justinditrani.bsky.social final postdoc paper (with contributions from many others) we show that forming/purifying vesicles (here from M. smegmatis) allows structure det'n of *endogenous* membrane proteins in their *native lipid bilayer*
🧵 on methods & TB biology...
www.pnas.org/doi/full/10....

I think people both within science and outside science don’t fully appreciate the miracle that were the Covid-19 vaccines. How much courage it took to get the sequence out, how much work had already gone into figuring out the best viral antigen and how best to present it. 1/

Mycobacterium leprae (leprosy) is alive and well as a neglected disease.
M. leprae lacks Cyt. bd, which should make it vulnerable to Cyt. bcc-aa3 inhibitors like Telacebec (Q203; currently in Phase 2 for TB, despite an obvious liability).
Also lacks Complex I, making NDH-2 inhibitors interesting.

New preprint!
@zestytoast.bsky.social provides the missing puzzle piece for a structural model of the mycobacterial OxPhos: NDH-2
We show the enzyme forms a dimer resembling eukaryotic, not prokaryotic, NDH-2s, and explain the SAR of a promising class of inhibitors.

www.biorxiv.org/content/10.1...

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

Happy to share my first ever (co)last author paper 🥳 reporting on how Mtb adapts its carbon diet under acid stress. A big thank you to my partners in crime @saehrt.bsky.social and @healycl.bsky.social without who this would not have been possible 😘
journals.asm.org/doi/10.1128/...

Our paper on high-resolution #cryoEM of the human CDK-activating kinase for structure-based drug design has been published in Nature Communications! We determined more than a dozen 2 Å structures of the ligand-bound complex to investigate the mechanism of inhibitor selectivity.

Years after the idea and preliminary experiments, Claire Coupland's amazing structure of the endogenous vacuolar- or vesicular-ATPase in its NATIVE vesicle is now in bioRxiv "High resolution cryo-EM of V-ATPase in native synaptic vesicles"
www.biorxiv.org/content/10.1...

Now out in Nature Comms!
Sarah Bickers (Kanelis lab and Rubinstein lab) determines the structure of the *dimeric* form of the ABC protein Ycf1p.
www.nature.com/articles/s41...