2BKQ

NEDD8 protease

2BKQ の概要

• エントリーDOI: 10.2210/pdb2bkq/pdb
• 関連するPDBエントリー: 1XT9 2BKR
• 分子名称: SENTRIN-SPECIFIC PROTEASE 8 (2 entities in total)
• 機能のキーワード: ubiquitin, hydrolase, protease, thiol protease, ubl conjugation pathway, ubiquitin-hydrolase complex
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 96292.66

構造登録者

Shen, L.N.,Liu, H.,Dong, C.,Xirodimas, D.,Naismith, J.H.,Hay, R.T. (登録日: 2005-02-18, 公開日: 2005-02-21, 最終更新日: 2024-05-08)

主引用文献

Shen, L.N.,Liu, H.,Dong, C.,Xirodimas, D.,Naismith, J.H.,Hay, R.T.
Structural Basis of Nedd8 Ubiquitin Discrimination by the Deneddylating Enzyme Nedp1
Embo J., 24:1341-, 2005

PubMed Abstract: NEDD8 (neural precursor cell expressed developmentally downregulated gene 8)-specific protease NEDP1 processes preNEDD8 to its mature form and deconjugates NEDD8 from substrates such as p53 and cullins. Although NEDD8 and ubiquitin are highly related in sequence and structure, their attachment to a protein leads to different biological effects. It is therefore critical that NEDP1 discriminates between NEDD8 and ubiquitin, and this requires remarkable precision in molecular recognition. To determine the basis of this specificity, we have determined the crystal structure of NEDP1 in isolation and in a transition state complex with NEDD8. This reveals that NEDP1 is a cysteine protease of the Ulp family. Binding of NEDD8 induces a dramatic conformational change in a flexible loop that swings over the C-terminus of NEDD8 locking it into an extended beta-structure optimal for catalysis. Structural, mutational and biochemical studies have identified key residues involved in molecular recognition. A single-residue difference in the C-terminus of NEDD8 and ubiquitin contributes significantly to the ability of NEDP1 to discriminate between them. In vivo analysis indicates that NEDP1 mutants perturb deNEDDylation of the tumour suppressor p53.

PubMed: 15775960
DOI: 10.1038/SJ.EMBOJ.7600628

実験手法

X-RAY DIFFRACTION (2 Å)