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Hydrolase(serine protease) PDB id
1pk4
Jmol
Contents
Protein chain
79 a.a. *
Ligands
SO4
Waters ×96
* Residue conservation analysis
PDB id:
1pk4
Name: Hydrolase(serine protease)
Title: Crystal and molecular structure of human plasminogen kringle 4 refined at 1.9-angstroms resolution
Structure: Plasminogen kringle 4. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
1.90Å     R-factor:   0.142    
Authors: A.Tulinsky,A.M.Mulichak
Key ref:
A.M.Mulichak et al. (1991). Crystal and molecular structure of human plasminogen kringle 4 refined at 1.9-A resolution. Biochemistry, 30, 10576-10588. PubMed id: 1657148 DOI: 10.1021/bi00107a029
Date:
18-Jul-91     Release date:   31-Oct-93    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00747  (PLMN_HUMAN) -  Plasminogen
Seq:
Struc: 		 
Seq:
Struc: 		810 a.a.
79 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.21.7  - Plasmin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Lys-|-Xaa > Arg-|-Xaa; higher selectivity than trypsin. Converts fibrin into soluble products.

 

 
DOI no: 10.1021/bi00107a029 Biochemistry 30:10576-10588 (1991)
PubMed id: 1657148  
 
 
Crystal and molecular structure of human plasminogen kringle 4 refined at 1.9-A resolution.
A.M.Mulichak, A.Tulinsky, K.G.Ravichandran.
 
  ABSTRACT  
 
The crystal structure of human plasminogen kringle 4 (PGK4) has been solved by molecular replacement using the bovine prothrombin kringle 1 (PTK1) structure as a model and refined by restrained least-squares methods to an R factor of 14.2% at 1.9-A resolution. The K4 structure is similar to that of PTK1, and an insertion of one residue at position 59 of the latter has minimal effect on the protein folding. The PGK4 structure is highly stabilized by an internal hydrophobic core and an extensive hydrogen-bonding network. Features new to this kringle include a cis peptide bond at Pro30 and the presence of two alternate, perpendicular, and equally occupied orientations for the Cys75 side chain. The K4 lysine-binding site consists of a hydrophobic trough formed by the Trp62 and Trp72 indole rings, with anionic (Asp55/Asp57) and cationic (Lys35/Arg71) charge pairs at either end. With the adjacent Asp5 and Arg32 residues, these result in triply charged anionic and cationic clusters (pH of crystals at 6.0), which, in addition to the unusually high accessibility of the Trp72 side chain, serve as an obvious marker of the binding site on the K4 surface. A complex intermolecular interaction occurs between the binding sites of symmetry-related molecules involving a highly ordered sulfate anion of solvation in which the Arg32 side chain of a neighboring kringle occupies the binding site.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21194375 J.H.Ahn, H.J.Lee, E.K.Lee, H.K.Yu, T.H.Lee, Y.Yoon, S.J.Kim, and J.S.Kim (2011).
Antiangiogenic kringles derived from human plasminogen and apolipoprotein(a) inhibit fibrinolysis through a mechanism that requires a functional lysine-binding site.
  Biol Chem, 392, 347-356.  
19593387 J.A.Kornblatt (2009).
Reduction of canine plasminogen leads to an expanded molecule which precipitates.
  PLoS One, 4, e6196.  
19524679 O.A.Ozhogina, and E.L.Bominaar (2009).
Characterization of the kringle fold and identification of a ubiquitous new class of disulfide rotamers.
  J Struct Biol, 168, 223-233.  
18956887 O.A.Ozhogina, A.Grishaev, E.L.Bominaar, L.Patthy, M.Trexler, and M.Llinás (2008).
NMR solution structure of the neurotrypsin Kringle domain.
  Biochemistry, 47, 12290-12298.
PDB codes: 2k4r 2k51
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.  
15018898 Y.Cao (2004).
Antiangiogenic cancer therapy.
  Semin Cancer Biol, 14, 139-145.  
11856839 M.C.Abad, and J.Geiger (2002).
Crystallization and preliminary X-ray diffraction studies of human angiostatin.
  Acta Crystallogr D Biol Crystallogr, 58, 513-514.  
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
12530539 N.R.Caterer, J.H.Graversen, C.Jacobsen, S.K.Moestrup, B.W.Sigurskjold, M.Etzerodt, and H.C.Thøgersen (2002).
Specificity determinants in the interaction of apolipoprotein(a) kringles with tetranectin and LDL.
  Biol Chem, 383, 1743-1750.  
12081498 S.Braud, B.F.Le Bonniec, C.Bon, and A.Wisner (2002).
The stratagem utilized by the plasminogen activator from the snake Trimeresurus stejnegeri to escape serpins.
  Biochemistry, 41, 8478-8484.  
11742690 K.Lähteenmäki, P.Kuusela, and T.K.Korhonen (2001).
Bacterial plasminogen activators and receptors.
  FEMS Microbiol Rev, 25, 531-552.  
11369850 Q.Ye, M.N.Rahman, M.L.Koschinsky, and Z.Jia (2001).
High-resolution crystal structure of apolipoprotein(a) kringle IV type 7: insights into ligand binding.
  Protein Sci, 10, 1124-1129.
PDB code: 1i71
10962086 J.A.Kornblatt (2000).
Understanding the fluorescence changes of human plasminogen when it binds the ligand, 6-aminohexanoate: a synthesis.
  Biochim Biophys Acta, 1481, 1.  
10428809 S.L.Nilsen, M.Prorok, and F.J.Castellino (1999).
Enhancement through mutagenesis of the binding of the isolated kringle 2 domain of human plasminogen to omega-amino acid ligands and to an internal sequence of a Streptococcal surface protein.
  J Biol Chem, 274, 22380-22386.  
10408340 Y.Chang, S.L.Nilsen, and F.J.Castellino (1999).
Functional and structural consequences of aromatic residue substitutions within the kringle-2 domain of tissue-type plasminogen activator.
  J Pept Res, 53, 656-664.  
9808033 C.T.Esmon, and T.Mather (1998).
Switching serine protease specificity.
  Nat Struct Biol, 5, 933-937.  
  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
9239402 N.W.Boonmark, X.J.Lou, Z.J.Yang, K.Schwartz, J.L.Zhang, E.M.Rubin, and R.M.Lawn (1997).
Modification of apolipoprotein(a) lysine binding site reduces atherosclerosis in transgenic mice.
  J Clin Invest, 100, 558-564.  
9294116 S.D.Hughes, X.J.Lou, S.Ighani, J.Verstuyft, D.J.Grainger, R.M.Lawn, and E.M.Rubin (1997).
Lipoprotein(a) vascular accumulation in mice. In vivo analysis of the role of lysine binding sites using recombinant adenovirus.
  J Clin Invest, 100, 1493-1500.  
9258400 T.Huby, J.Chapman, and J.Thillet (1997).
Pathophysiological implication of the structural domains of lipoprotein(a).
  Atherosclerosis, 133, 1-6.  
9278456 Y.Cao, A.Chen, S.S.An, R.W.Ji, D.Davidson, and M.Llinás (1997).
Kringle 5 of plasminogen is a novel inhibitor of endothelial cell growth.
  J Biol Chem, 272, 22924-22928.  
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.  
8910613 Y.Cao, R.W.Ji, D.Davidson, J.Schaller, D.Marti, S.Söhndel, S.G.McCance, M.S.O'Reilly, M.Llinás, and J.Folkman (1996).
Kringle domains of human angiostatin. Characterization of the anti-proliferative activity on endothelial cells.
  J Biol Chem, 271, 29461-29467.  
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.  
7742349 A.M.Scanu, and C.Edelstein (1995).
Kringle-dependent structural and functional polymorphism of apolipoprotein (a).
  Biochim Biophys Acta, 1256, 1.  
7629099 E.Bendixen, P.C.Harpel, and L.Sottrup-Jensen (1995).
Location of the major epsilon-(gamma-glutamyl)lysyl cross-linking site in transglutaminase-modified human plasminogen.
  J Biol Chem, 270, 17929-17933.  
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.  
  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
8423225 A.M.Scanu, L.A.Miles, G.M.Fless, D.Pfaffinger, J.Eisenbart, E.Jackson, J.L.Hoover-Plow, T.Brunck, and E.F.Plow (1993).
Rhesus monkey lipoprotein(a) binds to lysine Sepharose and U937 monocytoid cells less efficiently than human lipoprotein(a). Evidence for the dominant role of kringle 4(37).
  J Clin Invest, 91, 283-291.  
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 codes are shown on the right.