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" |