By the same authors

From the same journal

From the same journal

Increase of enzyme activity through specific covalent modification with fragments

Research output: Contribution to journalArticlepeer-review

Full text download(s)

Published copy (DOI)



Publication details

JournalChemical Science
DateAccepted/In press - 26 Sep 2017
DateE-pub ahead of print - 27 Sep 2017
DatePublished (current) - 1 Nov 2017
Issue number11
Number of pages8
Pages (from-to)7772-7779
Early online date27/09/17
Original languageEnglish


Modulation of enzyme activity is a powerful means of probing cellular function and can be exploited for diverse applications. Here, we explore a method of enzyme activation where covalent tethering of a small molecule to an enzyme can increase catalytic activity (k cat/K M) up to 35-fold. Using a bacterial glycoside hydrolase, BtGH84, we demonstrate how small molecule "fragments", identified as activators in free solution, can be covalently tethered to the protein using Michael-addition chemistry. We show how tethering generates a constitutively-activated enzyme-fragment conjugate, which displays both improved catalytic efficiency and increased susceptibility to certain inhibitor classes. Structure guided modifications of the tethered fragment demonstrate how specific interactions between the fragment and the enzyme influence the extent of activation. This work suggests that a similar approach may be used to modulate the activity of enzymes such as to improve catalytic efficiency or increase inhibitor susceptibility.

Bibliographical note

© The Royal Society of Chemistry 2017.


Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations