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

被引：69

作者：

Reverter, D

Wu, K

Erdene, TG

Pan, ZQ

Wilkinson, KD

Lima, CD ^{[1
]}

机构：

[1] Sloan Kettering Inst, Struct Biol Program, New York, NY 10021 USA

[2] Mt Sinai Med Ctr, Derald H Ruttenberg Canc Ctr, New York, NY 10029 USA

[3] Emory Univ, Sch Med, Atlanta, GA 30322 USA

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2005年 / 345卷 / 01期

基金：

美国国家卫生研究院;

关键词：

X-ray structure; cysteine protease; ubiquitin-like; Nedd8; Ulp family;

D O I：

10.1016/j.jmb.2004.10.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：141 / 151

页数：11

共 51 条

[1] Analysis of the deubiquitinating enzymes of the yeast Saccharomyces cerevisiae [J].