Activity-based diubiquitin probes for elucidating the linkage specificity of deubiquitinating enzymes.

Chem Commun (Camb)

Department of Chemistry and Biochemistry, University of Delaware, 214A Drake Hall, Newark, DE 19716, USA.

Published: January 2014

We report a new class of deubiquitinating enzyme (DUB) probes that resemble the native diubiquitin with a same linkage size and contain a Michael addition acceptor for trapping the DUB active-site cysteine. Both K63- and K48-linked diubiquitin probes were generated using a facile chemical ligation method. The diUb probes were demonstrated to label DUBs from different families and revealed intrinsic linkage specificities of DUBs.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918478PMC
http://dx.doi.org/10.1039/c3cc47382aDOI Listing

Publication Analysis

Top Keywords

diubiquitin probes
8
activity-based diubiquitin
4
probes
4
probes elucidating
4
elucidating linkage
4
linkage specificity
4
specificity deubiquitinating
4
deubiquitinating enzymes
4
enzymes report
4
report class
4

Similar Publications

Deubiquitinating enzymes are key regulators in the ubiquitin system and an emerging class of drug targets. These proteases disassemble polyubiquitin chains and many deubiquitinases show selectivity for specific polyubiquitin linkages. However, most biochemical insights originate from studies of single diubiquitin linkages in isolation, whereas in cells all linkages coexist.

View Article and Find Full Text PDF

Deubiquitinylating enzymes (DUBs) regulate the deubiquitinylation process of post-translationally modified proteins and thus control protein signaling in various cellular processes. The DUB Cezanne-1 catalyzes the cleavage of the iso-peptide bond of Lys11-linked polyubiquitin chains with high selectivity. Crystal structures of Cezanne-1 in different states provide important insight regarding the complex formation and global changes during the catalytic cycle but are lacking details of dynamics and control of activation.

View Article and Find Full Text PDF

Met1-specific motifs conserved in OTUB subfamily of green plants enable rice OTUB1 to hydrolyse Met1 ubiquitin chains.

Nat Commun

August 2022

Key Laboratory of Molecular Medicine and Biotherapy in the Ministry of Industry and Information Technology, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing, 100081, PR China.

Linear (Met1-linked) ubiquitination is involved inflammatory and innate immune signaling. Previous studies have characterized enzymes regulating the addition and removal of this modification in mammalian systems. However, only a few plant-derived deubiquitinases targeting Met1-linked ubiquitin chains have been reported and their mechanism of action remains elusive.

View Article and Find Full Text PDF

Probing the cell delivery of synthetic diubiquitin chains.

Chem Commun (Camb)

August 2022

Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel.

In this study, the live-cell delivery of structurally different synthetic diubiquitin chains was examined. We found that the combination of structural variations of the Ub chains (intrinsic factors); nature of CPP and CPP-protein linkage (extrinsic factors) influence their delivery.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!