We have located links that may give you full text access.
Reprogramming a Deubiquitinase into a Transamidase.
ACS Chemical Biology 2018 September 22
Access to well-defined ubiquitin conjugates has been key to elucidating the biochemical functions of proteins in the ubiquitin signaling network. Yet, we have a poor understanding of how deubiquitinases and ubiquitin-binding proteins respond to ubiquitin modifications when anchored to a protein other than ubiquitin or a ubiquitin-like protein. This is due to the difficulty of synthesizing ubiquitinated proteins comprised of native isopeptide bonds. Here we report on the evolution of a deubiquitinase capable of site-specifically modifying itself with defined ubiquitin chains. Following mutagenesis and yeast display screening, we identify a variant of the yeast ubiquitin C-terminal hydrolase Yuh1 that has a 28-fold improvement in the transamidation to hydrolysis ratio relative to the wild type enzyme. The switch in activity enables robust autoubiquitination of a lysine in the crossover loop to form an isopeptide bond. We demonstrate the utility of autoubiquitinating the evolved Yuh1 variant by investigating the consequences of ubiquitin chain anchoring on the activities of other deubiquitinases. Much to our surprise, we find that certain deubiquitinases are exquisitely sensitive to chain anchoring. These results highlight the importance of investigating the biochemical activities of deubiquitinases with both substrate-anchored and unanchored ubiquitin chains.
Full text links
Related Resources
Trending Papers
Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.Journal of Personalized Medicine 2024 Februrary 4
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.International Journal of Molecular Sciences 2024 April 4
The 'Ten Commandments' for the 2023 European Society of Cardiology guidelines for the management of endocarditis.European Heart Journal 2024 April 18
A Guide to the Use of Vasopressors and Inotropes for Patients in Shock.Journal of Intensive Care Medicine 2024 April 14
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app