Thanks for attaching the article! Here is what I took away:

They synthesized a tryptamine derivative called propyl dimethyl amino tryptamine (PDAT).

PDAT was able to inhibit INMT selectively, i.e. it did not inhibit 2 other methyltransferases they tested.

This in turn indicated the presence of an inhibitory allosteric site, so they used in silico computer modelling to find out where that site might be on the INMT molecule. They found a site that looks like can dock both PDAT and DMT which would explain the physical mechanism behind why DMT itself inhibits INMT as does the PDAT.


My take is that this could be the mechanism behind how the "small protein" or other substance from the original studies was inhibiting INMT. (Given that DMT itself proved inhibitory I wonder if it even had to be a "small protein" or rather just a "small molecule". I do recall though reading *somewhere* though that they had measured its molecular weight indirectly somehow and said it was a peptide.)

Out of the 60 or so references, one that might be worth following for a similar allosteric inhibitory process is this paper describing inhibition of protein arginine methyltransferase 3 (PRMT3):

https://www.ncbi.nlm.nih.gov/pubmed/22795084

https://www.researchgate...nsferase_in_rabbit_brain

A peptide-like inhibitor of N-methyltransferase in rabbit brain

I may have missed this in the posted references previously, but I didn't see it on first glance.
I don't have access to full text right now.

If there is this peptide-based inhibition of INMT, in addition to its regulation by small molecules like DMT or some metabolite, wouldn't it in theory be possible to use a yeast two-hybrid assay to figure out who is interacting with INMT? Or some other sort of pull down assay?

I am not sure how well they characterized the peptide in this paper beyond the molecular weights, activities and the fact that the fragment retained activity after digestion.

I've also only partly read Cozzi's paper so far.

Marzullo, Giovanni, Helen Rosengarten, and Arnold J. Friedhoff. "A peptide-like inhibitor of N-methyltransferase in rabbit brain." Life sciences 20.5 (1977): 775-783.

Much appreciated on the prompt retrieval dreamer!