Structure of a complex between Nedd8 and the Ulp/Senp protease family member Den1 Journal Article


Authors: Reverter, D.; Wu, K.; Erdene, T. G.; Pan, Z. Q.; Wilkinson, K. D.; Lima, C. D.
Article Title: Structure of a complex between Nedd8 and the Ulp/Senp protease family member Den1
Abstract: The Nedd8 conjugation pathway is conserved from yeast to humans and is essential in many organisms. Nedd8 is conjugated to cullin proteins in a process that alters SCF E3 ubiquitin ligase activity, and it is presumed that Nedd8 deconjugation would reverse these effects. We now report the X-ray structures of the human Nedd8-specific protease, Den1, in a complex with the inhibitor Nedd8 aldehyde, thus revealing a model for the tetrahedral transition state intermediate generated during proteolysis. Although Den1 is closely related to the SUMO-specific protease family (Ulp/Senp family), structural analysis of the interface suggests determinants involved in Nedd8 selectivity by Den1 over other ubiquitin-like family members and suggests how the Ulp/Senp architecture has been modified to interact with different ubiquitin-like modifiers. © 2004 Elsevier Ltd. All rights reserved.
Keywords: unclassified drug; protein conformation; complex formation; protein degradation; protein protein interaction; protein binding; amino acid sequence; molecular sequence data; sequence alignment; nucleotide sequence; crystal structure; models, molecular; crystallography, x-ray; protein family; structure analysis; isoprotein; macromolecular substances; ubiquitins; endopeptidases; x-ray structure; ubiquitin-like; nedd8; cysteine proteinase; nedd8 protein; cysteine protease; ulp family; protein den1; protein ulp
Journal Title: Journal of Molecular Biology
Volume: 345
Issue: 1
ISSN: 0022-2836
Publisher: Academic Press Inc., Elsevier Science  
Date Published: 2005-01-07
Start Page: 141
End Page: 151
Language: English
DOI: 10.1016/j.jmb.2004.10.022
PUBMED: 15567417
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 33" - "Export Date: 24 October 2012" - "CODEN: JMOBA" - "Molecular Sequence Numbers: GENBANK: AY008293;" - "Source: Scopus"
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  1. Christopher D Lima
    100 Lima