ArticleChembiochem : a European journal of chemical biology2013
Phage display to identify Nedd8-mimicking peptides as inhibitors of the Nedd8 transfer cascade.
Article in Chembiochem : a European journal of chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Integrated transcriptomic and proteomic analyses of plerocercoid and adult Spirometra mansoni reveal potential important pathways in the development of the medical tapeworm.Parasites & vectors · 2023Article
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- Small molecules targeting the NEDD8·NAE protein-protein interaction.Chemical science · 2020Article
- Protein Engineering in the Ubiquitin System: Tools for Discovery and Beyond.Pharmacological reviews · 2020Review
- Ubiquitin-Mimicking Peptides Transfer Differentiates by E1 and E2 Enzymes.BioMed research international · 2018Article
- SUMO-mimicking peptides inhibiting protein SUMOylation.Chembiochem : a European journal of chemical biology · 2014Article
- Synthesis and screening of peptide libraries with free C-termini.Current topics in peptide & protein research · 2014Article
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Authors and funding
7 authors.
Funding
Abstract
The Nedd8 activating enzyme (NAE) launches the transfer of the ubiquitin-like protein Nedd8 through an enzymatic cascade to covalently modify a diverse array of proteins, thus regulating their biological functions in the cell. The C-terminal peptide of Nedd8 extends deeply into the active site of NAE and plays an important role in the specific recognition of Nedd8 by NAE. We used phage display to profile C-terminal mutant sequences of Nedd8 that could be recognized by NAE for the activation reaction. We found that NAE can accommodate diverse changes in the Nedd8 C-terminal sequence (⁷¹ LALRGG⁷⁶), including Arg and Ile replacing Leu71, Leu, Ser, and Gln replacing Ala72, and substitutions by bulky aromatic residues at positions 73 and 74. We also observed that short peptides corresponding to the C-terminal sequences of the Nedd8 variants can be activated by NAE to form peptide~NAE thioester conjugates. Once NAE is covalently loaded with these Nedd8-mimicking peptides, it can no longer activate full-length Nedd8 for transfer to the neddylation targets, such as the cullin subunits of cullin-RING E3 ubiquitin ligases (CRLs). We have thus developed a new method to inhibit protein neddylation by Nedd8-mimicking peptides.
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Registered trials
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