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PDBsum entry 1jrr

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protein ligands Protein-protein interface(s) links
Peptide binding protein PDB id
1jrr
Jmol
Contents
Protein chains
357 a.a. *
15 a.a. *
Ligands
BME
Waters ×438
* Residue conservation analysis
PDB id:
1jrr
Name: Peptide binding protein
Title: Human plasminogen activator inhibitor-2.[Loop (66-98) deletionmutant] complexed with peptide mimicking the reactive center loop
Structure: Plasminogen activator inhibitor-2. Chain: a. Engineered: yes. Mutation: yes. Plasminogen activator inhibitor-2. Chain: p. Fragment: residues 367-380. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this sequence occurs naturally in humans
Biol. unit: Tetramer (from PQS)
Resolution:
1.60Å     R-factor:   0.198     R-free:   0.225
Authors: L.Jankova,S.J.Harrop,D.N.Saunders,J.L.Andrews,K.C.Bertram, A.R.Gould,M.S.Baker,P.M.G.Curmi
Key ref:
L.Jankova et al. (2001). Crystal structure of the complex of plasminogen activator inhibitor 2 with a peptide mimicking the reactive center loop. J Biol Chem, 276, 43374-43382. PubMed id: 11546761 DOI: 10.1074/jbc.M103021200
Date:
15-Aug-01     Release date:   26-Sep-01    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P05120  (PAI2_HUMAN) -  Plasminogen activator inhibitor 2
Seq:
Struc:
415 a.a.
357 a.a.
Protein chain
Pfam   ArchSchema ?
P05120  (PAI2_HUMAN) -  Plasminogen activator inhibitor 2
Seq:
Struc:
415 a.a.
14 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   4 terms 
  Biological process     wound healing   7 terms 
  Biochemical function     peptidase inhibitor activity     2 terms  

 

 
DOI no: 10.1074/jbc.M103021200 J Biol Chem 276:43374-43382 (2001)
PubMed id: 11546761  
 
 
Crystal structure of the complex of plasminogen activator inhibitor 2 with a peptide mimicking the reactive center loop.
L.Jankova, S.J.Harrop, D.N.Saunders, J.L.Andrews, K.C.Bertram, A.R.Gould, M.S.Baker, P.M.Curmi.
 
  ABSTRACT  
 
The structure of the serpin, plasminogen activator inhibitor type-2 (PAI-2), in a complex with a peptide mimicking its reactive center loop (RCL) has been determined at 1.6-A resolution. The structure shows the relaxed state serpin structure with a prominent six-stranded beta-sheet. Clear electron density is seen for all residues in the peptide. The P1 residue of the peptide binds to a well defined pocket at the base of PAI-2 that may be important in determining the specificity of protease inhibition. The stressed-to-relaxed state (S --> R) transition in PAI-2 can be modeled as the relative motion between a quasirigid core domain and a smaller segment comprising helix hF and beta-strands s1A, s2A, and s3A. A comparison of the Ramachandran plots of the stressed and relaxed state PAI-2 structures reveals the location of several hinge regions connecting these two domains. The hinge regions cluster in three locations on the structure, ensuring a cooperative S --> R transition. We hypothesize that the hinge formed by the conserved Gly(206) on beta-strand s3A in the breach region of PAI-2 effects the S --> R transition by altering its backbone torsion angles. This torsional change is due to the binding of the P14 threonine of the RCL to the open breach region of PAI-2.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Structure of the RCL peptide bound to PAI-2. A, the stereo figure shows the P14 site occupied by the RCL peptide. The P14 threonine side chain makes a hydrogen bond to the side chain of Tyr258, while the backbone of P14 makes two hydrogen bonds to Gly206. The side chain of Trp208 is anchored in the body of the protein and makes a hydrogen bond via its side chain with Asn363. The N-terminal acetyl group of the peptide makes a hydrogen bond to the backbone amide of Asn363, mimicking the RCL backbone. B, the stereogram shows the well formed P1 binding site, containing arginine P1 from the peptide. The side chain of P1 is stabilized by a network of hydrogen bonds to the backbone of PAI-2. This site is on the surface of the molecule.
Figure 4.
Fig. 4. Hinge regions in the S R transition in PAI-2. The structural changes that occur when PAI-2 goes from the stressed to the relaxed state are measured by examining changes in the Ramachandran plot. These are quantified by measuring a "distance" traveled in Ramachandran space by a residue as it goes from the stressed to the relaxed state structure. A, a plot of Ramachandran distance for all residues in the stressed and relaxed state PAI-2 structures. Six large changes are observed in the vicinity of residues: Ala^135, Ser151, Glu187, Gly260, Lys299, and Asn347. B, a Ramachandran diagram plotting the - transitions for residues undergoing a large torsional change (Ramachandran distance > 50°). The direction of the arrow indicates the transition from the stressed to the relaxed state conformation. C, a stereogram overlaying the backbone structure of the stressed state (red) and the relaxed state (green) of PAI-2. All residues that undergo a change in Ramachandran space greater than 30° are colored blue on the relaxed state structure.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 43374-43382) copyright 2001.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19245336 B.Gooptu, and D.A.Lomas (2009).
Conformational pathology of the serpins: themes, variations, and therapeutic strategies.
  Annu Rev Biochem, 78, 147-176.  
19442270 B.J.Cochran, L.P.Gunawardhana, K.L.Vine, J.A.Lee, S.Lobov, and M.Ranson (2009).
The CD-loop of PAI-2 (SERPINB2) is redundant in the targeting, inhibition and clearance of cell surface uPA activity.
  BMC Biotechnol, 9, 43.  
18548086 D.R.Croucher, D.N.Saunders, S.Lobov, and M.Ranson (2008).
Revisiting the biological roles of PAI2 (SERPINB2) in cancer.
  Nat Rev Cancer, 8, 535-545.  
18436534 S.H.Li, N.V.Gorlatova, D.A.Lawrence, and B.S.Schwartz (2008).
Structural differences between active forms of plasminogen activator inhibitor type 1 revealed by conformationally sensitive ligands.
  J Biol Chem, 283, 18147-18157.  
16634887 V.Oji, M.E.Oji, N.Adamini, T.Walker, K.Aufenvenne, M.Raghunath, and H.Traupe (2006).
Plasminogen activator inhibitor-2 is expressed in different types of congenital ichthyosis: in vivo evidence for its cross-linking into the cornified cell envelope by transglutaminase-1.
  Br J Dermatol, 154, 860-867.  
14567688 G.E.Blouse, M.J.Perron, J.O.Kvassman, S.Yunus, J.H.Thompson, R.L.Betts, L.C.Lutter, and J.D.Shore (2003).
Mutation of the highly conserved tryptophan in the serpin breach region alters the inhibitory mechanism of plasminogen activator inhibitor-1.
  Biochemistry, 42, 12260-12272.  
12682008 M.Wilczynska, S.Lobov, P.I.Ohlsson, and T.Ny (2003).
A redox-sensitive loop regulates plasminogen activator inhibitor type 2 (PAI-2) polymerization.
  EMBO J, 22, 1753-1761.  
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.