PDBsum entry 1ki0

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protein ligands links
Hydrolase PDB id
Protein chain
253 a.a. *
BCN ×3
Waters ×393
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: The x-ray structure of human angiostatin
Structure: Angiostatin. Chain: a. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: pichia pastoris. Expression_system_taxid: 4922
1.75Å     R-factor:   0.196     R-free:   0.263
Authors: M.C.Abad,R.K.Arni,D.K.Grella,F.J.Castellino,A.Tulinsky, J.H.Geiger
Key ref:
M.C.Abad et al. (2002). The X-ray crystallographic structure of the angiogenesis inhibitor angiostatin. J Mol Biol, 318, 1009-1017. PubMed id: 12054798 DOI: 10.1016/S0022-2836(02)00211-5
02-Dec-01     Release date:   29-May-02    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00747  (PLMN_HUMAN) -  Plasminogen
810 a.a.
253 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Plasmin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Lys-|-Xaa > Arg-|-Xaa; higher selectivity than trypsin. Converts fibrin into soluble products.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     blood coagulation   2 terms 
  Biochemical function     calcium ion binding     2 terms  


DOI no: 10.1016/S0022-2836(02)00211-5 J Mol Biol 318:1009-1017 (2002)
PubMed id: 12054798  
The X-ray crystallographic structure of the angiogenesis inhibitor angiostatin.
M.C.Abad, R.K.Arni, D.K.Grella, F.J.Castellino, A.Tulinsky, J.H.Geiger.
Angiogenesis inhibitors have gained much public attention recently as anti-cancer agents and several are currently in clinical trials, including angiostatin (Phase I, Thomas Jefferson University Hospital, Philadelphia, PA). We report here the bowl-shaped structure of angiostatin kringles 1-3, the first multi-kringle structure to be determined. All three kringle lysine-binding sites contain a bound bicine molecule of crystallization while the former of kringle 2 and kringle 3 are cofacial. Moreover, the separation of the kringle 2 and kringle 3 lysiner binding sites is sufficient to accommodate the alpha-helix of the 30 residue peptide VEK-30 found in the kringle 2/VEK-30 complex. Together the three kringles produce a central cavity suggestive of a unique domain where they may function in concert.
  Selected figure(s)  
Figure 4.
Figure 4. Stereoview of a Ribbons depiction of the modeled angiostatin/VEK-30 complex. The K2 of the K2/VEK-30 complex was overlaid on angiostatin K2 by C^a superposition as implemented in TURBO FRODO. Angiostatin is colored green while VEK-30 is colored lavender. Side-groups are labeled appropriately.
Figure 5.
Figure 5. GRASP drawing of the electrostatic potential surface (EPS) of angiostatin K1-3 (bicine omitted) corresponding to the orientation in Figure 1. EPS >10kT/e, blue; < -10kT/e, red; EPS vert, similar 0, white; (10kT vert, similar 6 kcal/mol). The most outstanding electronic feature is the highly electropositive LBS of K3 (LBS3) containing six electropositive residues; the bipolar nature of the K2 LBS is also conspicuous as is the overall neutrality of the back face of K1. Inspection of the other discoid face reveals: (1) the dipolar K1 LBS; (2) an electronegative charge cluster corresponding to the K1-K2 linker; and (3) the non-polar faces of K2 and K3. In addition, there is an electropositive crescent created by R223 and R242 of K2 that reinforces the positive K3 LBS.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 318, 1009-1017) copyright 2002.  
  Figures were selected by an automated process.  

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.  
20383568 A.Albini, S.Indraccolo, D.M.Noonan, and U.Pfeffer (2010).
Functional genomics of endothelial cells treated with anti-angiogenic or angiopreventive drugs.
  Clin Exp Metastasis, 27, 419-439.  
19800007 M.Wang, J.Zajicek, J.H.Geiger, M.Prorok, and F.J.Castellino (2010).
Solution structure of the complex of VEK-30 and plasminogen kringle 2.
  J Struct Biol, 169, 349-359.
PDB code: 2kj4
20028034 R.N.Bohnsack, M.Patel, L.J.Olson, S.S.Twining, and N.M.Dahms (2010).
Residues essential for plasminogen binding by the cation-independent mannose 6-phosphate receptor.
  Biochemistry, 49, 635-644.  
20939100 S.Kalkhof, S.Haehn, M.Paulsson, N.Smyth, J.Meiler, and A.Sinz (2010).
Computational modeling of laminin N-terminal domains using sparse distance constraints from disulfide bonds and chemical cross-linking.
  Proteins, 78, 3409-3427.  
20112045 S.S.Gerber, S.Lejon, M.Locher, and J.Schaller (2010).
The human alpha(2)-plasmin inhibitor: functional characterization of the unique plasmin(ogen)-binding region.
  Cell Mol Life Sci, 67, 1505-1518.  
19144161 A.Albini, C.Brigati, A.Ventura, G.Lorusso, M.Pinter, M.Morini, A.Mancino, A.Sica, and D.M.Noonan (2009).
Angiostatin anti-angiogenesis requires IL-12: The innate immune system as a key target.
  J Transl Med, 7, 5.  
19363026 A.J.Cork, S.Jergic, S.Hammerschmidt, B.Kobe, V.Pancholi, J.L.Benesch, C.V.Robinson, N.E.Dixon, J.A.Aquilina, and M.J.Walker (2009).
Defining the structural basis of human plasminogen binding by streptococcal surface enolase.
  J Biol Chem, 284, 17129-17137.  
19593387 J.A.Kornblatt (2009).
Reduction of canine plasminogen leads to an expanded molecule which precipitates.
  PLoS One, 4, e6196.  
19052322 S.Hong, and P.L.Pedersen (2008).
ATP synthase and the actions of inhibitors utilized to study its roles in human health, disease, and other scientific areas.
  Microbiol Mol Biol Rev, 72, 590.  
  19662173 J.A.Kornblatt, T.A.Barretto, K.Chigogidze, and B.Chirwa (2007).
Canine plasminogen: spectral responses to changes in 6-aminohexanoate and temperature.
  Anal Chem Insights, 2, 17-29.  
16991168 F.Grandi, M.Sandal, G.Guarguaglini, E.Capriotti, R.Casadio, and B.Samorì (2006).
Hierarchical mechanochemical switches in angiostatin.
  Chembiochem, 7, 1774-1782.  
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.  
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.