PDBsum entry 1xt9

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protein Protein-protein interface(s) links
Hydrolase/hydrolase inhibitor PDB id
Jmol PyMol
Protein chains
208 a.a. *
76 a.a. *
Waters ×100
* Residue conservation analysis
PDB id:
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)
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
21-Oct-04     Release date:   21-Dec-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q96LD8  (SENP8_HUMAN) -  Sentrin-specific protease 8
212 a.a.
208 a.a.
Protein chain
Pfam   ArchSchema ?
Q15843  (NEDD8_HUMAN) -  NEDD8
81 a.a.
76 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain A: E.C.  - Ulp1 peptidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular vesicular exosome   3 terms 
  Biological process     anatomical structure morphogenesis   11 terms 
  Biochemical function     hydrolase activity     9 terms  


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.
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.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19571111 K.D.Wilkinson (2009).
DUBs at a glance.
  J Cell Sci, 122, 2325-2329.  
19186998 Z.Xu, H.Y.Chan, W.L.Lam, K.H.Lam, L.S.Lam, T.B.Ng, and S.W.Au (2009).
SUMO proteases: redox regulation and biological consequences.
  Antioxid Redox Signal, 11, 1453-1484.  
18799455 C.D.Lima, and D.Reverter (2008).
Structure of the Human SENP7 Catalytic Domain and Poly-SUMO Deconjugation Activities for SENP6 and SENP7.
  J Biol Chem, 283, 32045-32055.
PDB code: 3eay
18274552 D.P.Xirodimas, A.Sundqvist, A.Nakamura, L.Shen, C.Botting, and R.T.Hay (2008).
Ribosomal proteins are targets for the NEDD8 pathway.
  EMBO Rep, 9, 280-286.  
18802447 G.Rabut, and M.Peter (2008).
Function and regulation of protein neddylation. 'Protein modifications: beyond the usual suspects' review series.
  EMBO Rep, 9, 969-976.  
18652489 J.Souphron, M.B.Waddell, A.Paydar, Z.Tokgöz-Gromley, M.F.Roussel, and B.A.Schulman (2008).
Structural dissection of a gating mechanism preventing misactivation of ubiquitin by NEDD8's E1.
  Biochemistry, 47, 8961-8969.
PDB codes: 3dbh 3dbl 3dbr
18666185 M.Drag, and G.S.Salvesen (2008).
DeSUMOylating enzymes--SENPs.
  IUBMB Life, 60, 734-742.  
18492068 Z.Tang, C.M.Hecker, A.Scheschonka, and H.Betz (2008).
Protein interactions in the sumoylation cascade: lessons from X-ray structures.
  FEBS J, 275, 3003-3015.  
17591783 J.Mikolajczyk, M.Drag, M.Békés, J.T.Cao, Z.Ronai, and G.S.Salvesen (2007).
Small ubiquitin-related modifier (SUMO)-specific proteases: profiling the specificities and activities of human SENPs.
  J Biol Chem, 282, 26217-26224.  
17960327 V.Katritch, C.M.Byrd, V.Tseitin, D.Dai, E.Raush, M.Totrov, R.Abagyan, R.Jordan, and D.E.Hruby (2007).
Discovery of small molecule inhibitors of ubiquitin-like poxvirus proteinase I7L using homology modeling and covalent docking approaches.
  J Comput Aided Mol Des, 21, 549-558.  
17597129 X.Zhu, R.Ménard, and T.Sulea (2007).
High incidence of ubiquitin-like domains in human ubiquitin-specific proteases.
  Proteins, 69, 1-7.  
  20103862 Y.Chen (2007).
The enzymes in ubiquitin-like post-translational modifications.
  Biosci Trends, 1, 16-25.  
16608434 B.M.Kessler (2006).
Putting proteomics on target: activity-based profiling of ubiquitin and ubiquitin-like processing enzymes.
  Expert Rev Proteomics, 3, 213-221.  
16608850 L.Gong, and E.T.Yeh (2006).
Characterization of a family of nucleolar SUMO-specific proteases with preference for SUMO-2 or SUMO-3.
  J Biol Chem, 281, 15869-15877.  
17099698 L.Shen, M.H.Tatham, C.Dong, A.Zagórska, J.H.Naismith, and R.T.Hay (2006).
SUMO protease SENP1 induces isomerization of the scissile peptide bond.
  Nat Struct Mol Biol, 13, 1069-1077.
PDB codes: 2iy0 2iy1
16913834 T.Sulea, H.A.Lindner, and R.Ménard (2006).
Structural aspects of recently discovered viral deubiquitinating activities.
  Biol Chem, 387, 853-862.  
16183633 K.Sugawara, N.N.Suzuki, Y.Fujioka, N.Mizushima, Y.Ohsumi, and F.Inagaki (2005).
Structural basis for the specificity and catalysis of human Atg4B responsible for mammalian autophagy.
  J Biol Chem, 280, 40058-40065.
PDB code: 2cy7
15775960 L.N.Shen, H.Liu, C.Dong, D.Xirodimas, J.H.Naismith, and R.T.Hay (2005).
Structural basis of NEDD8 ubiquitin discrimination by the deNEDDylating enzyme NEDP1.
  EMBO J, 24, 1341-1351.
PDB codes: 2bkq 2bkr
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.