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Plasminogen activator PDB id
1tpk
Jmol
Contents
Protein chains
88 a.a. *
Metals
_CL ×3
Waters ×91
* Residue conservation analysis
PDB id:
1tpk
Name: Plasminogen activator
Title: Crystal structure of the kringle-2 domain of tissue plasmino activator at 2.4-angstroms resolution
Structure: Tissue plasminogen activator. Chain: a, b, c. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
2.40Å     R-factor:   0.184    
Authors: A.M.De Vos,M.H.Ultsch,R.F.Kelley,K.Padmanabhan,A.Tulinsky, M.L.Westbrook,A.A.Kossiakoff
Key ref:
A.M.de Vos et al. (1992). Crystal structure of the kringle 2 domain of tissue plasminogen activator at 2.4-A resolution. Biochemistry, 31, 270-279. PubMed id: 1310033 DOI: 10.1021/bi00116a037
Date:
24-Sep-91     Release date:   15-Jul-92    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00750  (TPA_HUMAN) -  Tissue-type plasminogen activator
Seq:
Struc: 		 
Seq:
Struc: 		562 a.a.
88 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.21.68  - T-plasminogen activator.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.

 

 
DOI no: 10.1021/bi00116a037 Biochemistry 31:270-279 (1992)
PubMed id: 1310033  
 
 
Crystal structure of the kringle 2 domain of tissue plasminogen activator at 2.4-A resolution.
A.M.de Vos, M.H.Ultsch, R.F.Kelley, K.Padmanabhan, A.Tulinsky, M.L.Westbrook, A.A.Kossiakoff.
 
  ABSTRACT  
 
The crystal structure of the kringle 2 domain of tissue plasminogen activator was determined and refined at a resolution of 2.43 A. The overall fold of the molecule is similar to that of prothrombin kringle 1 and plasminogen kringle 4; however, there are differences in the lysine binding pocket, and two looping regions, which include insertions in kringle 2, take on very different conformations. Based on a comparison of the overall structural homology between kringle 2 and kringle 4, a new sequence alignment for kringle domains is proposed that results in a division of kringle domains into two groups, consistent with their proposed evolutionary relation. The crystal structure shows a strong interaction between a lysine residue of one molecule and the lysine/fibrin binding pocket of a noncrystallographically related neighbor. This interaction represents a good model of a bound protein ligand and is the first such ligand that has been observed in a kringle binding pocket. The structure shows an intricate network of interactions both among the binding pocket residues and between binding pocket residues and the lysine ligand. A lysine side chain is identified as the positively charged group positioned to interact with the carboxylate of lysine and lysine analogue ligands. In addition, a chloride ion is located in the kringle-kringle interface and contributes to the observed interaction between kringle molecules.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21136135 J.Schaller, and S.S.Gerber (2011).
The plasmin-antiplasmin system: structural and functional aspects.
  Cell Mol Life Sci, 68, 785-801.  
19492051 J.Stie, G.Bruni, and D.Fox (2009).
Surface-associated plasminogen binding of Cryptococcus neoformans promotes extracellular matrix invasion.
  PLoS One, 4, e5780.  
15140132 G.Epple, W.D.Schleuning, G.Kettelgerdes, E.Kottgen, R.Gessner, and M.Praus (2004).
Prion protein stimulates tissue-type plasminogen activator-mediated plasmin generation via a lysine-binding site on kringle 2.
  J Thromb Haemost, 2, 962-968.  
14717962 J.H.Geiger, and S.E.Cnudde (2004).
What the structure of angiostatin may tell us about its mechanism of action.
  J Thromb Haemost, 2, 23-34.  
12529357 K.S.Kim, Y.K.Hong, Y.A.Joe, Y.Lee, J.Y.Shin, H.E.Park, I.H.Lee, S.Y.Lee, D.K.Kang, S.I.Chang, and S.I.Chung (2003).
Anti-angiogenic activity of the recombinant kringle domain of urokinase and its specific entry into endothelial cells.
  J Biol Chem, 278, 11449-11456.  
12564979 Y.J.Park, J.F.Liang, H.Song, Y.T.Li, S.Naik, and V.C.Yang (2003).
ATTEMPTS: a heparin/protamine-based triggered release system for the delivery of enzyme drugs without associated side-effects.
  Adv Drug Deliv Rev, 55, 251-265.  
11928808 M.Gehrmann, K.Briknarová, L.Bányai, L.Patthy, and M.Llinás (2002).
The col-1 module of human matrix metalloproteinase-2 (MMP-2): structural/functional relatedness between gelatin-binding fibronectin type II modules and lysine-binding kringle domains.
  Biol Chem, 383, 137-148.
PDB code: 1ks0
  9524060 M.T.Stubbs, M.Renatus, and W.Bode (1998).
An active zymogen: unravelling the mystery of tissue-type plasminogen activator.
  Biol Chem, 379, 95.  
  9817840 M.Ultsch, N.A.Lokker, P.J.Godowski, and A.M.de Vos (1998).
Crystal structure of the NK1 fragment of human hepatocyte growth factor at 2.0 A resolution.
  Structure, 6, 1383-1393.
PDB code: 1bht
  9761475 S.S.An, D.N.Marti, C.Carreño, F.Albericio, J.Schaller, and M.Llinas (1998).
Structural/functional properties of the Glu1-HSer57 N-terminal fragment of human plasminogen: conformational characterization and interaction with kringle domains.
  Protein Sci, 7, 1947-1959.  
9258400 T.Huby, J.Chapman, and J.Thillet (1997).
Pathophysiological implication of the structural domains of lipoprotein(a).
  Atherosclerosis, 133, 1-6.  
9434908 W.Bode, and M.Renatus (1997).
Tissue-type plasminogen activator: variants and crystal/solution structures demarcate structural determinants of function.
  Curr Opin Struct Biol, 7, 865-872.  
8663495 A.A.Higazi, T.Ganz, K.Kariko, and D.B.Cines (1996).
Defensin modulates tissue-type plasminogen activator and plasminogen binding to fibrin and endothelial cells.
  J Biol Chem, 271, 17650-17655.  
8838586 J.Guevara, N.V.Valentinova, O.Garcia, A.M.Gotto, C.Y.Yang, S.Legal, J.Gaubatz, and J.T.Sparrow (1996).
Interaction of apolipoprotein[a] with apolipoproteinB-100 Cys3734 region in lipoprotein[a] is confirmed immunochemically.
  J Protein Chem, 15, 17-25.  
8735839 O.Zhao, and I.M.Kovach (1996).
Reversible modification of tissue-type plasminogen activator by methylphosphonate esters.
  Bioorg Med Chem, 4, 523-529.  
8870072 P.Bork, A.K.Downing, B.Kieffer, and I.D.Campbell (1996).
Structure and distribution of modules in extracellular proteins.
  Q Rev Biophys, 29, 119-167.  
7890760 A.Ernst, M.Helmhold, C.Brunner, A.Pethö-Schramm, V.W.Armstrong, and H.J.Müller (1995).
Identification of two functionally distinct lysine-binding sites in kringle 37 and in kringles 32-36 of human apolipoprotein(a).
  J Biol Chem, 270, 6227-6234.  
7759476 A.H.Bakker, E.J.Weening-Verhoeff, and J.H.Verheijen (1995).
The role of the lysyl binding site of tissue-type plasminogen activator in the interaction with a forming fibrin clot.
  J Biol Chem, 270, 12355-12360.  
7852411 K.Mori, R.A.Dwek, A.K.Downing, G.Opdenakker, and P.M.Rudd (1995).
The activation of type 1 and type 2 plasminogen by type I and type II tissue plasminogen activator.
  J Biol Chem, 270, 3261-3267.  
7711052 P.M.Rudd, R.J.Woods, M.R.Wormald, G.Opdenakker, A.K.Downing, I.D.Campbell, and R.A.Dwek (1995).
The effects of variable glycosylation on the functional activities of ribonuclease, plasminogen and tissue plasminogen activator.
  Biochim Biophys Acta, 1248, 1.  
  7546567 R.C.Ladner (1995).
Constrained peptides as binding entities.
  Trends Biotechnol, 13, 426-430.  
8170967 B.A.Keyt, N.F.Paoni, C.J.Refino, L.Berleau, H.Nguyen, A.Chow, J.Lai, L.Peña, C.Pater, and J.Ogez (1994).
A faster-acting and more potent form of tissue plasminogen activator.
  Proc Natl Acad Sci U S A, 91, 3670-3674.  
8307012 D.Marti, J.Schaller, B.Ochensberger, and E.E.Rickli (1994).
Expression, purification and characterization of the recombinant kringle 2 and kringle 3 domains of human plasminogen and analysis of their binding affinity for omega-aminocarboxylic acids.
  Eur J Biochem, 219, 455-462.  
  7764899 I.D.Campbell, and A.K.Downing (1994).
Building protein structure and function from modular units.
  Trends Biotechnol, 12, 168-172.  
  7756992 L.E.Donate, E.Gherardi, N.Srinivasan, R.Sowdhamini, S.Aparicio, and T.L.Blundell (1994).
Molecular evolution and domain structure of plasminogen-related growth factors (HGF/SF and HGF1/MSP).
  Protein Sci, 3, 2378-2394.  
8181475 M.R.Rejante, and M.Llinás (1994).
1H-NMR assignments and secondary structure of human plasminogen kringle 1.
  Eur J Biochem, 221, 927-937.  
8181476 M.R.Rejante, and M.Llinás (1994).
Solution structure of the epsilon-aminohexanoic acid complex of human plasminogen kringle 1.
  Eur J Biochem, 221, 939-949.
PDB codes: 1hpj 1hpk
  8069624 C.A.Orengo, and J.M.Thornton (1993).
Alpha plus beta folds revisited: some favoured motifs.
  Structure, 1, 105-120.  
8386013 J.Guevara, J.Spurlino, A.Y.Jan, C.Y.Yang, A.Tulinsky, B.V.Prasad, J.W.Gaubatz, and J.D.Morrisett (1993).
Proposed mechanisms for binding of apo[a] kringle type 9 to apo B-100 in human lipoprotein[a].
  Biophys J, 64, 686-700.  
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.