In which we find the new tricks an old dog can do

We all know that the carboxy terminal glycine of ubiquitin forms an amide with with the epsilon amino group of lysine.  Like a double play in baseball, 3 enzymes are involved, which move ubiquitin to E1 (the shortstop) to E2 (the second baseman) to E3 (the first baseman).  We have over 600 E3 enzymes, 40 E2s and 9 E1s.

A new paper [ Nature vol. 556 pp. 381 – 385 ’18 ] describes an E3 enzyme (called MYCBP2 aka PHR1) with a different specificity — it forms esters between the carboxy terminal glycine of ubiquitin and the hydroxyl group of serine or threonine.  The authors speculate a bit, noting that there are a lot of hydroxyl groups around in the cell that aren’t on proteins — sugars and lipids come to mind.   Just how widespread this is and whether any of the other 600 E3’s have similar activity isn’t known.

So now we have yet another new (to us) player in the metabolic life of the cell. It is yet another post-translational protein modification.   The enzyme is found in neurons, making understanding the workings of the brain even harder.