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PDBsum entry 2j7q
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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
2j7q

 

 

 

 

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Contents
Protein chains
232 a.a. *
75 a.a. *
Ligands
GVE ×2
PG4
GOL
Metals
_MG ×3
Waters ×707
* Residue conservation analysis
PDB id:
2j7q
Name: Hydrolase
Title: Crystal structure of the ubiquitin-specific protease encoded by murine cytomegalovirus tegument protein m48 in complex with a ubquitin-based suicide substrate
Structure: Mcmv tegument protein m48 encoded ubiquitin- specific protease, m48usp. Chain: a. Engineered: yes. Other_details: deubiquitinating module of murine cytomegalovirus tegument protein m48. Active site cysteine 23 is covalently linked to the former vinylmethylester moiety of the suicide substate ubvme. Ubiquitin. Chain: b, d.
Source: Murine cytomegalovirus. Organism_taxid: 10366. Strain: mcmv strain smith. Atcc: vr-1399. Expressed in: escherichia coli. Expression_system_taxid: 469008. Homo sapiens. Human. Organism_taxid: 9606.
Resolution:
1.80Å     R-factor:   0.157     R-free:   0.214
Authors: C.Schlieker,W.A.Weihofen,E.Frijns,L.M.Kattenhorn,R.Gaudet,H.L.Ploegh
Key ref:
C.Schlieker et al. (2007). Structure of a herpesvirus-encoded cysteine protease reveals a unique class of deubiquitinating enzymes. Mol Cell, 25, 677-687. PubMed id: 17349955 DOI: 10.1016/j.molcel.2007.01.033
Date:
16-Oct-06     Release date:   20-Mar-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
No UniProt id for this chain
Struc: 232 a.a.
Protein chains
Pfam   ArchSchema ?
P0CG48  (UBC_HUMAN) -  Polyubiquitin-C from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		685 a.a.
75 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains B, D: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1016/j.molcel.2007.01.033 Mol Cell 25:677-687 (2007)
PubMed id: 17349955  
 
 
Structure of a herpesvirus-encoded cysteine protease reveals a unique class of deubiquitinating enzymes.
C.Schlieker, W.A.Weihofen, E.Frijns, L.M.Kattenhorn, R.Gaudet, H.L.Ploegh.
 
  ABSTRACT  
 
All members of the herpesviridae contain within their large tegument protein a cysteine protease module that displays deubiquitinating activity. We report the crystal structure of the cysteine protease domain of murine cytomegalovirus M48 (M48(USP)) in a complex with a ubiquitin (Ub)-based suicide substrate. M48(USP) adopts a papain-like fold, with the active-site cysteine forming a thioether linkage to the suicide substrate. The Ub core participates in an extensive hydrophobic interaction with an exposed beta hairpin loop of M48(USP). This Ub binding mode contributes to Ub specificity and is distinct from that observed in other deubiquitinating enzymes. Both the arrangement of active-site residues and the architecture of the interface with Ub lead us to classify this domain as the founding member of a previously unknown class of deubiquitinating enzymes.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Fold and Structure of M48^USP-UbVME
(A) Ribbon representation of the M48^USP structure (gray with the β hairpin in orange) in complex with UbVME (green). The secondary structure elements are labeled, and the side chains of catalytic triad residues are shown in yellow.
(B) Electrostatic surface potential representation of M48^USP with bound Ub shown in a ribbon representation (top). Below, Ub, in an electrostatic surface potential representation, was rotated 180° to show the charge distribution on the face forming the interface. Note the charge complementarity between the M48^USP acidic cleft and the positively charged Ub C terminus.
(C) The final 2F[o] − F[c] electron density map contoured at 1.3 σ indicates a covalent bond between the catalytic C23 and the Cβ atom of the former vinylmethylester moiety at the Ub C terminus.
Figure 3.
Figure 3. Interactions between UbVME and M48^USP
(A) Stereo view of the extended C terminus and attached VME moiety of Ub in the M48^USP active-site cleft. M48^USP and UbVME are in gray and green, respectively. Nitrogen atoms are shown in blue, and oxygen atoms in red. Dashed lines indicate hydrogen bonds. Note that the Ub C terminus features an extended β conformation and is extensively coordinated by several hydrogen bonds to M48^USP residues. V140 and Y76 of M48^USP are in van der Waals contact and form a canopy over the active site.
(B) Stereo view of the interactions between the Ub core (green) and M48^USP (gray) or its β hairpin (orange). The gray transparent M48^USP surface highlights the shape complementarity of the interface, which is mainly lined by hydrophobic residues.
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2007, 25, 677-687) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21242292 D.K.Stringer, and R.C.Piper (2011).
A single ubiquitin is sufficient for cargo protein entry into MVBs in the absence of ESCRT ubiquitination.
  J Cell Biol, 192, 229-242.  
20042598 K.Artavanis-Tsakonas, W.A.Weihofen, J.M.Antos, B.I.Coleman, C.A.Comeaux, M.T.Duraisingh, R.Gaudet, and H.L.Ploegh (2010).
Characterization and structural studies of the Plasmodium falciparum ubiquitin and Nedd8 hydrolase UCHL3.
  J Biol Chem, 285, 6857-6866.
PDB codes: 2wdt 2we6
20190741 S.Gastaldello, S.Hildebrand, O.Faridani, S.Callegari, M.Palmkvist, C.Di Guglielmo, and M.G.Masucci (2010).
A deneddylase encoded by Epstein-Barr virus promotes viral DNA replication by regulating the activity of cullin-RING ligases.
  Nat Cell Biol, 12, 351-361.  
19759126 E.T.Kim, S.E.Oh, Y.O.Lee, W.Gibson, and J.H.Ahn (2009).
Cleavage specificity of the UL48 deubiquitinating protease activity of human cytomegalovirus and the growth of an active-site mutant virus in cultured cells.
  J Virol, 83, 12046-12056.  
19404332 F.Randow, and P.J.Lehner (2009).
Viral avoidance and exploitation of the ubiquitin system.
  Nat Cell Biol, 11, 527-534.  
19382171 G.Nicastro, L.Masino, V.Esposito, R.P.Menon, A.De Simone, F.Fraternali, and A.Pastore (2009).
Josephin domain of ataxin-3 contains two distinct ubiquitin-binding sites.
  Biopolymers, 91, 1203-1214.  
19381253 J.I.Lee, P.J.Sollars, S.B.Baver, G.E.Pickard, M.Leelawong, and G.A.Smith (2009).
A herpesvirus encoded deubiquitinase is a novel neuroinvasive determinant.
  PLoS Pathog, 5, e1000387.  
  19256548 K.R.Love, R.K.Pandya, E.Spooner, and H.L.Ploegh (2009).
Ubiquitin C-terminal electrophiles are activity-based probes for identification and mechanistic study of ubiquitin conjugating machinery.
  ACS Chem Biol, 4, 275-287.  
  19527883 M.K.Isaacson, and H.L.Ploegh (2009).
Ubiquitination, ubiquitin-like modifiers, and deubiquitination in viral infection.
  Cell Host Microbe, 5, 559-570.  
19047059 M.W.Popp, K.Artavanis-Tsakonas, and H.L.Ploegh (2009).
Substrate Filtering by the Active Site Crossover Loop in UCHL3 Revealed by Sortagging and Gain-of-function Mutations.
  J Biol Chem, 284, 3593-3602.  
19225106 Q.Yao, J.Cui, Y.Zhu, G.Wang, L.Hu, C.Long, R.Cao, X.Liu, N.Huang, S.Chen, L.Liu, and F.Shao (2009).
A bacterial type III effector family uses the papain-like hydrolytic activity to arrest the host cell cycle.
  Proc Natl Acad Sci U S A, 106, 3716-3721.
PDB codes: 3eir 3eit
19818707 R.Ernst, B.Mueller, H.L.Ploegh, and C.Schlieker (2009).
The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER.
  Mol Cell, 36, 28-38.  
19706716 S.Gredmark-Russ, M.K.Isaacson, L.Kattenhorn, E.J.Cheung, N.Watson, and H.L.Ploegh (2009).
A gammaherpesvirus ubiquitin-specific protease is involved in the establishment of murine gammaherpesvirus 68 infection.
  J Virol, 83, 10644-10652.  
19211026 T.Wang, L.Yin, E.M.Cooper, M.Y.Lai, S.Dickey, C.M.Pickart, D.Fushman, K.D.Wilkinson, R.E.Cohen, and C.Wolberger (2009).
Evidence for bidentate substrate binding as the basis for the K48 linkage specificity of otubain 1.
  J Mol Biol, 386, 1011-1023.  
18321862 B.H.Ha, H.C.Ahn, S.H.Kang, K.Tanaka, C.H.Chung, and E.E.Kim (2008).
Structural basis for Ufm1 processing by UfSP1.
  J Biol Chem, 283, 14893-14900.
PDB code: 2z84
19017811 C.D.Schlieker, A.G.Van der Veen, J.R.Damon, E.Spooner, and H.L.Ploegh (2008).
A functional proteomics approach links the ubiquitin-related modifier Urm1 to a tRNA modification pathway.
  Proc Natl Acad Sci U S A, 105, 18255-18260.  
18852458 K.Ratia, S.Pegan, J.Takayama, K.Sleeman, M.Coughlin, S.Baliji, R.Chaudhuri, W.Fu, B.S.Prabhakar, M.E.Johnson, S.C.Baker, A.K.Ghosh, and A.D.Mesecar (2008).
A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication.
  Proc Natl Acad Sci U S A, 105, 16119-16124.  
18346885 L.Song, and M.Rape (2008).
Reverse the curse--the role of deubiquitination in cell cycle control.
  Curr Opin Cell Biol, 20, 156-163.  
18715931 R.Sompallae, S.Gastaldello, S.Hildebrand, N.Zinin, G.Hassink, K.Lindsten, J.Haas, B.Persson, and M.G.Masucci (2008).
Epstein-barr virus encodes three bona fide ubiquitin-specific proteases.
  J Virol, 82, 10477-10486.  
18270205 T.E.Messick, N.S.Russell, A.J.Iwata, K.L.Sarachan, R.Shiekhattar, J.R.Shanks, F.E.Reyes-Turcu, K.D.Wilkinson, and R.Marmorstein (2008).
Structural basis for ubiquitin recognition by the Otu1 ovarian tumor domain protein.
  J Biol Chem, 283, 11038-11049.
PDB codes: 3by4 3c0r
17984316 H.Ploegh, and H.Ploegh (2007).
Hidde Ploegh: immunologist, journeyman. Interview by Nicole LeBrasseur.
  J Cell Biol, 179, 364-365.  
18056809 K.Jarosinski, L.Kattenhorn, B.Kaufer, H.Ploegh, and N.Osterrieder (2007).
A herpesvirus ubiquitin-specific protease is critical for efficient T cell lymphoma formation.
  Proc Natl Acad Sci U S A, 104, 20025-20030.  
17948018 K.R.Love, A.Catic, C.Schlieker, and H.L.Ploegh (2007).
Mechanisms, biology and inhibitors of deubiquitinating enzymes.
  Nat Chem Biol, 3, 697-705.  
17928337 S.Böttcher, H.Granzow, C.Maresch, B.Möhl, B.G.Klupp, and T.C.Mettenleiter (2007).
Identification of functional domains within the essential large tegument protein pUL36 of pseudorabies virus.
  J Virol, 81, 13403-13411.  
17634221 S.Gredmark, C.Schlieker, V.Quesada, E.Spooner, and H.L.Ploegh (2007).
A functional ubiquitin-specific protease embedded in the large tegument protein (ORF64) of murine gammaherpesvirus 68 is active during the course of infection.
  J Virol, 81, 10300-10309.  
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 codes are shown on the right.

 

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