A new Tool to Profile Proteoglycans & Goodbye Zhen

We're delighted to report a just-released preprint from the lab detailing a new chemical tool to profile proteoglycans; a glycan class which is crucial in many aspects of health and disease, yet notoriously difficult to study. Proteoglycans consist of a core protein decorated by glycosaminoglycan (GAG) chain(s). GAG biosynthesis is initiated by one of two xylsyltransferase (XT) isoenzymes in mammals, which accept the activated form of xylose (UDP-xylose) as a substrate. 

Mutants of both XT1 and XT2 were generated with a 'hole' in the active site which were able to accept a 'bumped' version of UDP-xylose (UDP-6AzGlc). This so-called 'bump-and-hole' (BH) pair was demonstrated to function in vitro. With some innovative chemistry, UDP-6AzGlc could also be used in living cells which had been transfected with mutant XT1/XT2 to profile protein substrates of these enzymes. You can learn more about the bump-and-hole technique which we employ extensively in the lab here. 

Check out the preprint here, and for a succinct summary, head to this Twitter/X thread written by Ben. 

This work is largely down an extraordinary effort from the paper's first author Zhen Li, who has a been a wonderful member of the lab over the last four years. Zhen says goodbye to the lab after watching it grow from almost the beginning! We wish her all the best in the future and are so glad she joined us 😊