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PDBsum entry 1r5x

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protein metals Protein-protein interface(s) links
Structural genomics, unknown function PDB id
1r5x
Jmol
Contents
Protein chains
103 a.a. *
Metals
_ZN ×2
Waters ×89
* Residue conservation analysis
PDB id:
1r5x
Name: Structural genomics, unknown function
Title: Jamm: a metalloprotease-like zinc site in the proteasome and signalosome
Structure: Afjamm. Chain: a, b. Engineered: yes
Source: Archaeoglobus fulgidus. Organism_taxid: 224325. Strain: dsm 4304. Gene: af2198. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.30Å     R-factor:   0.263     R-free:   0.308
Authors: X.I.Ambroggio,D.C.Rees,R.J.Deshaies
Key ref: X.I.Ambroggio et al. (2004). JAMM: a metalloprotease-like zinc site in the proteasome and signalosome. PLoS Biol, 2, E2. PubMed id: 14737182
Date:
13-Oct-03     Release date:   25-Nov-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O28085  (O28085_ARCFU) -  Uncharacterized protein
Seq:
Struc:
121 a.a.
103 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     metal ion binding     1 term  

 

 
PLoS Biol 2:E2 (2004)
PubMed id: 14737182  
 
 
JAMM: a metalloprotease-like zinc site in the proteasome and signalosome.
X.I.Ambroggio, D.C.Rees, R.J.Deshaies.
 
  ABSTRACT  
 
The JAMM (JAB1/MPN/Mov34 metalloenzyme) motif in Rpn11 and Csn5 underlies isopeptidase activities intrinsic to the proteasome and signalosome, respectively. We show here that the archaebacterial protein AfJAMM possesses the key features of a zinc metalloprotease, yet with a distinct fold. The histidine and aspartic acid of the conserved EX(n)HS/THX(7)SXXD motif coordinate a zinc, whereas the glutamic acid hydrogen-bonds an aqua ligand. By analogy to the active site of thermolysin, we predict that the glutamic acid serves as an acid-base catalyst and the second serine stabilizes a tetrahedral intermediate. Mutagenesis of Csn5 confirms these residues are required for Nedd8 isopeptidase activity. The active site-like architecture specified by the JAMM motif motivates structure-based approaches to the study of JAMM domain proteins and the development of therapeutic proteasome and signalosome inhibitors.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
22183254 J.Maupin-Furlow (2012).
Proteasomes and protein conjugation across domains of life.
  Nat Rev Microbiol, 10, 100-111.  
21283576 C.Luise, M.Capra, M.Donzelli, G.Mazzarol, M.G.Jodice, P.Nuciforo, G.Viale, P.P.Di Fiore, and S.Confalonieri (2011).
An atlas of altered expression of deubiquitinating enzymes in human cancer.
  PLoS One, 6, e15891.  
21169198 T.Nunoura, Y.Takaki, J.Kakuta, S.Nishi, J.Sugahara, H.Kazama, G.J.Chee, M.Hattori, A.Kanai, H.Atomi, K.Takai, and H.Takami (2011).
Insights into the evolution of Archaea and eukaryotic protein modifier systems revealed by the genome of a novel archaeal group.
  Nucleic Acids Res, 39, 3204-3223.  
21124883 J.Moretti, P.Chastagner, S.Gastaldello, S.F.Heuss, A.M.Dirac, R.Bernards, M.G.Masucci, A.Israël, and C.Brou (2010).
The translation initiation factor 3f (eIF3f) exhibits a deubiquitinase activity regulating Notch activation.
  PLoS Biol, 8, e1000545.  
20029420 M.S.Huen, S.M.Sy, and J.Chen (2010).
BRCA1 and its toolbox for the maintenance of genome integrity.
  Nat Rev Mol Cell Biol, 11, 138-148.  
20399188 R.I.Enchev, A.Schreiber, F.Beuron, and E.P.Morris (2010).
Structural insights into the COP9 signalosome and its common architecture with the 26S proteasome lid and eIF3.
  Structure, 18, 518-527.  
19261749 B.Wang, K.Hurov, K.Hofmann, and S.J.Elledge (2009).
NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control.
  Genes Dev, 23, 729-739.  
19214193 E.M.Cooper, C.Cutcliffe, T.Z.Kristiansen, A.Pandey, C.M.Pickart, and R.E.Cohen (2009).
K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated Brcc36 and proteasomal Poh1.
  EMBO J, 28, 621-631.  
19243136 F.E.Reyes-Turcu, and K.D.Wilkinson (2009).
Polyubiquitin binding and disassembly by deubiquitinating enzymes.
  Chem Rev, 109, 1495-1508.  
19202061 G.Shao, D.R.Lilli, J.Patterson-Fortin, K.A.Coleman, D.E.Morrissey, and R.A.Greenberg (2009).
The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks.
  Proc Natl Acad Sci U S A, 106, 3166-3171.  
19261746 G.Shao, J.Patterson-Fortin, T.E.Messick, D.Feng, N.Shanbhag, Y.Wang, and R.A.Greenberg (2009).
MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA double-strand breaks.
  Genes Dev, 23, 740-754.  
19231300 J.Hannah, and P.Zhou (2009).
Regulation of DNA damage response pathways by the cullin-RING ubiquitin ligases.
  DNA Repair (Amst), 8, 536-543.  
19295498 M.Rape (2009).
A set of surgical chain saws.
  EMBO J, 28, 615-616.  
19141280 M.Sharon, H.Mao, E.Boeri Erba, E.Stephens, N.Zheng, and C.V.Robinson (2009).
Symmetrical modularity of the COP9 signalosome complex suggests its multifunctionality.
  Structure, 17, 31-40.  
19826004 S.Cayli, J.Klug, J.Chapiro, S.Fröhlich, G.Krasteva, L.Orel, and A.Meinhardt (2009).
COP9 signalosome interacts ATP-dependently with p97/valosin-containing protein (VCP) and controls the ubiquitination status of proteins bound to p97/VCP.
  J Biol Chem, 284, 34944-34953.  
18199546 A.S.Adler, L.E.Littlepage, M.Lin, T.L.Kawahara, D.J.Wong, Z.Werb, and H.Y.Chang (2008).
CSN5 isopeptidase activity links COP9 signalosome activation to breast cancer progression.
  Cancer Res, 68, 506-515.  
18579431 B.Cvek, and Z.Dvorak (2008).
The value of proteasome inhibition in cancer. Can the old drug, disulfiram, have a bright new future as a novel proteasome inhibitor?
  Drug Discov Today, 13, 716-722.  
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.  
17879958 X.C.Zhang, J.Chen, C.H.Su, H.Y.Yang, and M.H.Lee (2008).
Roles for CSN5 in control of p53/MDM2 activities.
  J Cell Biochem, 103, 1219-1230.  
18758443 Y.Sato, A.Yoshikawa, A.Yamagata, H.Mimura, M.Yamashita, K.Ookata, O.Nureki, K.Iwai, M.Komada, and S.Fukai (2008).
Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains.
  Nature, 455, 358-362.
PDB codes: 2znr 2znv
17525341 B.Sobhian, G.Shao, D.R.Lilli, A.C.Culhane, L.A.Moreau, B.Xia, D.M.Livingston, and R.A.Greenberg (2007).
RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites.
  Science, 316, 1198-1202.  
17707232 P.Zhu, W.Zhou, J.Wang, J.Puc, K.A.Ohgi, H.Erdjument-Bromage, P.Tempst, C.K.Glass, and M.G.Rosenfeld (2007).
A histone H2A deubiquitinase complex coordinating histone acetylation and H1 dissociation in transcriptional regulation.
  Mol Cell, 27, 609-621.  
17470786 S.Busch, E.U.Schwier, K.Nahlik, O.Bayram, K.Helmstaedt, O.W.Draht, S.Krappmann, O.Valerius, W.N.Lipscomb, and G.H.Braus (2007).
An eight-subunit COP9 signalosome with an intact JAMM motif is required for fungal fruit body formation.
  Proc Natl Acad Sci U S A, 104, 8089-8094.  
17317632 V.Pena, S.Liu, J.M.Bujnicki, R.Lührmann, and M.C.Wahl (2007).
Structure of a multipartite protein-protein interaction domain in splicing factor prp8 and its link to retinitis pigmentosa.
  Mol Cell, 25, 615-624.
PDB code: 2og4
  20103862 Y.Chen (2007).
The enzymes in ubiquitin-like post-translational modifications.
  Biosci Trends, 1, 16-25.  
16890423 D.J.Rigden (2006).
Understanding the cell in terms of structure and function: insights from structural genomics.
  Curr Opin Biotechnol, 17, 457-464.  
16816840 G.Nalepa, M.Rolfe, and J.W.Harper (2006).
Drug discovery in the ubiquitin-proteasome system.
  Nat Rev Drug Discov, 5, 596-613.  
16569633 J.F.Nabhan, and P.Ribeiro (2006).
The 19 S proteasomal subunit POH1 contributes to the regulation of c-Jun ubiquitination, stability, and subcellular localization.
  J Biol Chem, 281, 16099-16107.  
16869714 M.Sharon, T.Taverner, X.I.Ambroggio, R.J.Deshaies, and C.V.Robinson (2006).
Structural organization of the 19S proteasome lid: insights from MS of intact complexes.
  PLoS Biol, 4, e267.  
16428608 P.Bellare, A.K.Kutach, A.K.Rines, C.Guthrie, and E.J.Sontheimer (2006).
Ubiquitin binding by a variant Jab1/MPN domain in the essential pre-mRNA splicing factor Prp8p.
  RNA, 12, 292-302.  
16274748 R.L.Neve, and D.L.McPhie (2006).
The cell cycle as a therapeutic target for Alzheimer's disease.
  Pharmacol Ther, 111, 99.  
16913834 T.Sulea, H.A.Lindner, and R.Ménard (2006).
Structural aspects of recently discovered viral deubiquitinating activities.
  Biol Chem, 387, 853-862.  
15904532 C.Zhou, F.Arslan, S.Wee, S.Krishnan, A.R.Ivanov, A.Oliva, J.Leatherwood, and D.A.Wolf (2005).
PCI proteins eIF3e and eIF3m define distinct translation initiation factor 3 complexes.
  BMC Biol, 3, 14.  
15822184 M.A.Correia, S.Sadeghi, and E.Mundo-Paredes (2005).
Cytochrome P450 ubiquitination: branding for the proteolytic slaughter?
  Annu Rev Pharmacol Toxicol, 45, 439-464.  
15688063 M.D.Petroski, and R.J.Deshaies (2005).
Function and regulation of cullin-RING ubiquitin ligases.
  Nat Rev Mol Cell Biol, 6, 9.  
16325574 S.M.Nijman, M.P.Luna-Vargas, A.Velds, T.R.Brummelkamp, A.M.Dirac, T.K.Sixma, and R.Bernards (2005).
A genomic and functional inventory of deubiquitinating enzymes.
  Cell, 123, 773-786.  
15314065 J.McCullough, M.J.Clague, and S.Urbé (2004).
AMSH is an endosome-associated ubiquitin isopeptidase.
  J Cell Biol, 166, 487-492.  
14737189 M.H.Glickman, and N.Adir (2004).
The proteasome and the delicate balance between destruction and rescue.
  PLoS Biol, 2, E13.  
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.