PDBsum entry 1xt9

Hydrolase/hydrolase inhibitor

PDB id: 1xt9

Contents

Protein chains

208 a.a. *

76 a.a. *

Waters ×100

* Residue conservation analysis

PDB id:

1xt9

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure of den1 in complex with nedd8

Structure:

Sentrin-specific protease 8. Chain: a. Synonym: sentrin/sumo-specific protease senp8, cysteine protease fksg8, protease, cysteine 2, den1 protease. Engineered: yes. Neddylin. Chain: b. Synonym: ubiquitin-like protein nedd8. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: senp8, fksg8, prsc2. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: glutathione s-transferase fusion, cleaved with thrombin. Gene: nedd8.

Biol. unit:

Dimer (from PQS)

Resolution:

2.20Å R-factor: 0.209 R-free: 0.259

Authors:

D.Reverter,K.Wu,T.G.Erdene,Z.Q.Pan,K.D.Wilkinson,C.D.Lima

Key ref:

D.Reverter et al. (2005). Structure of a complex between Nedd8 and the Ulp/Senp protease family member Den1. J Mol Biol, 345, 141-151. PubMed id: 15567417 DOI: 10.1016/j.jmb.2004.10.022

Date:

21-Oct-04 Release date: 21-Dec-04

Protein chain

Q96LD8  (SENP8_HUMAN) -  Sentrin-specific protease 8 from Homo sapiens

Seq: 212 a.a.

Struc: 208 a.a.

Protein chain

Q15843  (NEDD8_HUMAN) -  NEDD8 from Homo sapiens

Seq: 81 a.a.

Struc: 76 a.a.

Enzyme reactions

• Enzyme class: Chain A: E.C.3.4.22.- - ?????

DOI no: 10.1016/j.jmb.2004.10.022

J Mol Biol 345:141-151 (2005)

PubMed id: 15567417

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

D.Reverter, K.Wu, T.G.Erdene, Z.Q.Pan, K.D.Wilkinson, C.D.Lima.

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.

Selected figure(s)

Figure 2.
Figure 2. Structure of Den1-Nedd8. A, Ribbon representation of the secondary structure of the human Den1 in complex with Nedd8. b Strands from Den1 (yellow) and from Nedd8 (orange) are numbered and a helices from Den1 (pink) and from Nedd8 (red) are lettered. Den1 catalytic residues and the Nedd8 Gly-Gly motif are numbered and shown in bond representation. N and C termini of each polypeptide chain are labeled as N[t] or C[t], respectively. B, The 90° rotation of the ribbon representation shown in A. Graphics were prepared using Pymol unless otherwise noted.51

Figure 4.
Figure 4. Stereo representations of the Den1-Nedd8 interface. A, Stereo representation of the interaction between the Nedd8 C-terminal tail (gray) and Den1 (yellow). Residues involved in interaction with Nedd8 are labeled and shown in bond representation. Amino acid residues thought to participate in hydrogen bonding interactions between these two molecules are denoted by red broken lines. B, Stereo representation focusing on the interactions between Nedd8 (gray) and Den1 (yellow) that do not involve the Den1 catalytic residues. Amino acid residues involved in the interaction are labeled and shown in bond representation with hydrogen bonding patterns depicted as red broken lines. C, Stereo representation focusing on the interactions between Nedd8 (gray) and Den1 (yellow) that do not involve the Den1 catalytic residues. Amino acid residues involved in the interaction are labeled and shown in bond representation with hydrogen bonding patterns depicted as red broken lines.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 345, 141-151) copyright 2005.

Figures were selected by the author.