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PDBsum entry 2io2

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protein Protein-protein interface(s) links
Protein binding, hydrolase PDB id
2io2
Jmol
Contents
Protein chains
225 a.a. *
75 a.a. *
156 a.a. *
Waters ×8
* Residue conservation analysis
PDB id:
2io2
Name: Protein binding, hydrolase
Title: Crystal structure of human senp2 in complex with rangap1-sum
Structure: Sentrin-specific protease 2. Chain: a. Fragment: catalytic domain. Synonym: sentrin/sumo-specific protease senp2, smt3-specifi isopeptidase 2, smt3ip2, axam2. Engineered: yes. Mutation: yes. Small ubiquitin-related modifier 1. Chain: b.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: senp2, kiaa1331. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: sumo1, smt3c, smt3h3, ubl1. Gene: rangap1.
Biol. unit: Dodecamer (from PDB file)
Resolution:
2.90Å     R-factor:   0.268     R-free:   0.301
Authors: D.Reverter,C.D.Lima
Key ref:
D.Reverter and C.D.Lima (2006). Structural basis for SENP2 protease interactions with SUMO precursors and conjugated substrates. Nat Struct Mol Biol, 13, 1060-1068. PubMed id: 17099700 DOI: 10.1038/nsmb1168
Date:
09-Oct-06     Release date:   21-Nov-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9HC62  (SENP2_HUMAN) -  Sentrin-specific protease 2
Seq:
Struc:
 
Seq:
Struc:
589 a.a.
225 a.a.*
Protein chain
Pfam   ArchSchema ?
P63165  (SUMO1_HUMAN) -  Small ubiquitin-related modifier 1
Seq:
Struc:
101 a.a.
75 a.a.
Protein chain
Pfam   ArchSchema ?
Q9BSK3  (Q9BSK3_HUMAN) -  Putative uncharacterized protein (Fragment)
Seq:
Struc:
213 a.a.
156 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain A: E.C.3.4.22.68  - Ulp1 peptidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     signal transduction   2 terms 
  Biochemical function     cysteine-type peptidase activity     2 terms  

 

 
DOI no: 10.1038/nsmb1168 Nat Struct Mol Biol 13:1060-1068 (2006)
PubMed id: 17099700  
 
 
Structural basis for SENP2 protease interactions with SUMO precursors and conjugated substrates.
D.Reverter, C.D.Lima.
 
  ABSTRACT  
 
SUMO processing and deconjugation are essential proteolytic activities for nuclear metabolism and cell-cycle progression in yeast and higher eukaryotes. To elucidate the mechanisms used during substrate lysine deconjugation, SUMO isoform processing and SUMO isoform interactions, X-ray structures were determined for a catalytically inert SENP2 protease domain in complex with conjugated RanGAP1-SUMO-1 or RanGAP1-SUMO-2, or in complex with SUMO-2 or SUMO-3 precursors. Common features within the active site include a 90 degrees kink proximal to the scissile bond that forces C-terminal amino acid residues or the lysine side chain toward a protease surface that appears optimized for lysine deconjugation. Analysis of this surface reveals SENP2 residues, particularly Met497, that mediate, and in some instances reverse, in vitro substrate specificity. Mutational analysis and biochemistry provide a mechanism for SENP2 substrate preferences that explains why SENP2 catalyzes SUMO deconjugation more efficiently than processing.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Structures of SENP2 deconjugation complexes with RanGAP1–SUMO-1 and RanGAP1–SUMO-2. (a) Two nearly orthogonal views of the human SENP2 catalytic domain in complex with the C-terminal domain of RanGAP1 conjugated to either SUMO-2 (left) or SUMO-1 (right), shown as ribbons. SENP2 catalytic residues are shown in bond representation, as is the isopeptide bond between lysine and the SUMO diglycine motif. (b) Stereo representation of the interaction between the SUMO-1 C-terminal tail (yellow), SENP2 (blue) and the consensus residues of RanGAP1 (magenta), with interacting residues labeled and shown in bond representation. Red dashed lines denote putative hydrogen bonds. (c) Surface representation of SENP2 in complex with the consensus residues of RanGAP1 conjugated to the SUMO-1 diglycine motif. SUMO-1 C-terminal residues (yellow) and RanGAP1 consensus motif (magenta) are shown as sticks. (d) Stereo view of Ubc9 (SUMO E2, yellow) active site in complex with RanGAP1–SUMO-1 (PDB 1Z5S)^29, depicted as in b. (e) Simulated annealing omit map contoured at 1.2 , covering the isopeptide bond and selected active site residues in the SENP2–RanGAP1–SUMO-1 structure. Graphics prepared with PyMOL^41 (http://pymol.sourceforge.net).
Figure 5.
Figure 5. Comparison of the hydrogen bond coordination of the and peptide bonds in the deconjugation and processing complexes. (a) Stick representation of isopeptide bond between RanGAP1 Lys524 and SUMO Gly97. Blue, SENP2; yellow, SUMO; magenta, RanGAP1; red dashed lines, hydrogen bonds. (b) Stick representation of scissile peptide bond between Gly92 and Val93 from pre-SUMO-3, in similar orientation as in a.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2006, 13, 1060-1068) copyright 2006.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20087442 E.Van Damme, K.Laukens, T.H.Dang, and X.Van Ostade (2010).
A manually curated network of the PML nuclear body interactome reveals an important role for PML-NBs in SUMOylation dynamics.
  Int J Biol Sci, 6, 51-67.  
20663916 G.Fernández-Miranda, I.Pérez de Castro, M.Carmena, C.Aguirre-Portolés, S.Ruchaud, X.Fant, G.Montoya, W.C.Earnshaw, and M.Malumbres (2010).
SUMOylation modulates the function of Aurora-B kinase.
  J Cell Sci, 123, 2823-2833.  
21102611 J.R.Gareau, and C.D.Lima (2010).
The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition.
  Nat Rev Mol Cell Biol, 11, 861-871.  
20590526 N.Kolli, J.Mikolajczyk, M.Drag, D.Mukhopadhyay, N.Moffatt, M.Dasso, G.Salvesen, and K.D.Wilkinson (2010).
Distribution and paralogue specificity of mammalian deSUMOylating enzymes.
  Biochem J, 430, 335-344.  
19008217 E.T.Yeh (2009).
SUMOylation and De-SUMOylation: Wrestling with Life's Processes.
  J Biol Chem, 284, 8223-8227.  
19322194 K.Satoo, N.N.Noda, H.Kumeta, Y.Fujioka, N.Mizushima, Y.Ohsumi, and F.Inagaki (2009).
The structure of Atg4B-LC3 complex reveals the mechanism of LC3 processing and delipidation during autophagy.
  EMBO J, 28, 1341-1350.
PDB codes: 2z0d 2z0e 2zzp
19285941 S.Zhu, J.Goeres, K.M.Sixt, M.Békés, X.D.Zhang, G.S.Salvesen, and M.J.Matunis (2009).
Protection from isopeptidase-mediated deconjugation regulates paralog-selective sumoylation of RanGAP1.
  Mol Cell, 33, 570-580.  
19635839 W.A.Hofmann, A.Arduini, S.M.Nicol, C.J.Camacho, J.L.Lessard, F.V.Fuller-Pace, and P.de Lanerolle (2009).
SUMOylation of nuclear actin.
  J Cell Biol, 186, 193-200.  
19923268 Y.Wang, and M.Dasso (2009).
SUMOylation and deSUMOylation at a glance.
  J Cell Sci, 122, 4249-4252.  
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
18838537 L.A.Campbell, E.J.Faivre, M.D.Show, J.G.Ingraham, J.Flinders, J.D.Gross, and H.A.Ingraham (2008).
Decreased recognition of SUMO-sensitive target genes following modification of SF-1 (NR5A1).
  Mol Cell Biol, 28, 7476-7486.  
18666185 M.Drag, and G.S.Salvesen (2008).
DeSUMOylating enzymes--SENPs.
  IUBMB Life, 60, 734-742.  
17440617 A.Catic, S.Misaghi, G.A.Korbel, and H.L.Ploegh (2007).
ElaD, a Deubiquitinating protease expressed by E. coli.
  PLoS ONE, 2, e381.  
17466333 A.D.Capili, and C.D.Lima (2007).
Structure and analysis of a complex between SUMO and Ubc9 illustrates features of a conserved E2-Ubl interaction.
  J Mol Biol, 369, 608-618.
PDB code: 2pe6
17919899 A.D.Capili, and C.D.Lima (2007).
Taking it step by step: mechanistic insights from structural studies of ubiquitin/ubiquitin-like protein modification pathways.
  Curr Opin Struct Biol, 17, 726-735.  
17475278 D.M.Duda, R.C.van Waardenburg, L.A.Borg, S.McGarity, A.Nourse, M.B.Waddell, M.A.Bjornsti, and B.A.Schulman (2007).
Structure of a SUMO-binding-motif mimic bound to Smt3p-Ubc9p: conservation of a non-covalent ubiquitin-like protein-E2 complex as a platform for selective interactions within a SUMO pathway.
  J Mol Biol, 369, 619-630.
PDB code: 2eke
17499995 D.Mukhopadhyay, and M.Dasso (2007).
Modification in reverse: the SUMO proteases.
  Trends Biochem Sci, 32, 286-295.  
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.  
17146457 D.T.Huang, and B.A.Schulman (2006).
Breaking up with a kinky SUMO.
  Nat Struct Mol Biol, 13, 1045-1047.  
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.