PDBsum entry 5hpg

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protein Protein-protein interface(s) links
Serine protease PDB id
Protein chain
84 a.a. *
Waters ×193
* Residue conservation analysis
PDB id:
Name: Serine protease
Title: Structure and ligand determinants of the recombinant kringle 5 domain of human plasminogen
Structure: Plasminogen. Chain: a, b. Fragment: kringle 5. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
1.66Å     R-factor:   0.166    
Authors: A.Tulinsky,I.Mochalkin,F.J.Castellino
Key ref:
Y.Chang et al. (1998). Structure and ligand binding determinants of the recombinant kringle 5 domain of human plasminogen. Biochemistry, 37, 3258-3271. PubMed id: 9521645 DOI: 10.1021/bi972284e
19-Sep-97     Release date:   25-Mar-98    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P00747  (PLMN_HUMAN) -  Plasminogen
810 a.a.
84 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: 10.1021/bi972284e Biochemistry 37:3258-3271 (1998)
PubMed id: 9521645  
Structure and ligand binding determinants of the recombinant kringle 5 domain of human plasminogen.
Y.Chang, I.Mochalkin, S.G.McCance, B.Cheng, A.Tulinsky, F.J.Castellino.
The X-ray crystal structure of the recombinant (r) kringle 5 domain of human plasminogen (K5HPg) has been solved by molecular replacement methods using K1HPg as a model and refined at 1.7 A resolution to an R factor of 16.6%. The asymmetric unit of K5HPg is composed of two molecules related by a noncrystallographic 2-fold rotation axis approximately parallel to the z-direction. The lysine binding site (LBS) is defined by the regions His33-Thr37, Pro54-Val58, Pro61-Tyr64, and Leu71-Tyr74 and is occupied in the apo-form by water molecules. A unique feature of the LBS of apo-K5HPg is the substitution by Leu71 for the basic amino acid, arginine, that in other kringle polypeptides forms the donor cationic center for the carboxylate group of omega-amino acid ligands. While wild-type (wt) r-K5HPg interacted weakly with these types of ligands, replacement by site-directed mutagenesis of Leu71 by arginine led to substantially increased affinity of the ligands for the LBS of K5HPg. As a result, binding of omega-amino acids to this mutant kringle (r-K5HPg[L71R]) was restored to levels displayed by the companion much stronger affinity HPg kringles, K1HPg and K4HPg. Correspondingly, alkylamine binding to r-K5HPg[L71R] was considerably attenuated from that shown by wtr-K5HPg. Thus, employing a rational design strategy based on the crystal structure of K5HPg, successful remodeling of the LBS has been accomplished, and has resulted in the conversion of a weak ligand binding kringle to one that possesses an affinity for omega-amino acids that is similar to K1HPg and K4HPg.

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.  
20718867 K.Hasumi, S.Yamamichi, and T.Harada (2010).
Small-molecule modulators of zymogen activation in the fibrinolytic and coagulation systems.
  FEBS J, 277, 3675-3687.  
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
19473980 A.C.Tharp, M.Laha, P.Panizzi, M.W.Thompson, P.Fuentes-Prior, and P.E.Bock (2009).
Plasminogen Substrate Recognition by the Streptokinase-Plasminogen Catalytic Complex Is Facilitated by Arg253, Lys256, and Lys257 in the Streptokinase {beta}-Domain and Kringle 5 of the Substrate.
  J Biol Chem, 284, 19511-19521.  
19593387 J.A.Kornblatt (2009).
Reduction of canine plasminogen leads to an expanded molecule which precipitates.
  PLoS One, 4, e6196.  
  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.  
16109649 S.X.Zhang, J.Sima, J.J.Wang, C.Shao, J.Fant, and J.X.Ma (2005).
Systemic and periocular deliveries of plasminogen kringle 5 reduce vascular leakage in rat models of oxygen-induced retinopathy and diabetes.
  Curr Eye Res, 30, 681-689.  
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.  
15297465 M.E.Bulina, K.A.Lukyanov, I.V.Yampolsky, D.M.Chudakov, D.B.Staroverov, A.S.Shcheglov, N.G.Gurskaya, and S.Lukyanov (2004).
New class of blue animal pigments based on Frizzled and Kringle protein domains.
  J Biol Chem, 279, 43367-43370.  
12713905 P.J.Hogg (2003).
Disulfide bonds as switches for protein function.
  Trends Biochem Sci, 28, 210-214.  
12646571 S.C.Wu, F.J.Castellino, and S.L.Wong (2003).
A fast-acting, modular-structured staphylokinase fusion with Kringle-1 from human plasminogen as the fibrin-targeting domain offers improved clot lysis efficacy.
  J Biol Chem, 278, 18199-18206.  
11782484 A.J.Lay, X.M.Jiang, E.Daly, L.Sun, and P.J.Hogg (2002).
Plasmin reduction by phosphoglycerate kinase is a thiol-independent process.
  J Biol Chem, 277, 9062-9068.  
11876638 J.T.Douglas, P.D.von Haller, M.Gehrmann, M.Llinás, and J.Schaller (2002).
The two-domain NK1 fragment of plasminogen: folding, ligand binding, and thermal stability profile.
  Biochemistry, 41, 3302-3310.  
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
11297431 J.A.Kornblatt, I.Rajotte, and F.Heitz (2001).
Reaction of canine plasminogen with 6-aminohexanoate: a thermodynamic study combining fluorescence, circular dichroism, and isothermal titration calorimetry.
  Biochemistry, 40, 3639-3647.  
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.  
10858289 J.H.Graversen, B.W.Sigurskjold, H.C.Thøgersen, and M.Etzerodt (2000).
Tetranectin-binding site on plasminogen kringle 4 involves the lysine-binding pocket and at least one additional amino acid residue.
  Biochemistry, 39, 7414-7419.  
10625440 D.N.Marti, J.Schaller, and M.Llinás (1999).
Solution structure and dynamics of the plasminogen kringle 2-AMCHA complex: 3(1)-helix in homologous domains.
  Biochemistry, 38, 15741-15755.
PDB code: 1b2i
10026282 I.Mochalkin, B.Cheng, O.Klezovitch, A.M.Scanu, and A.Tulinsky (1999).
Recombinant kringle IV-10 modules of human apolipoprotein(a): structure, ligand binding modes, and biological relevance.
  Biochemistry, 38, 1990-1998.
PDB codes: 1kiv 3kiv 4kiv
10491165 J.A.Kornblatt, M.J.Kornblatt, C.Clery, and C.Balny (1999).
The effects of hydrostatic pressure on the conformation of plasminogen.
  Eur J Biochem, 265, 120-126.  
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.  
9783753 M.A.Parry, C.Fernandez-Catalan, A.Bergner, R.Huber, K.P.Hopfner, B.Schlott, K.H.Gührs, and W.Bode (1998).
The ternary microplasmin-staphylokinase-microplasmin complex is a proteinase-cofactor-substrate complex in action.
  Nat Struct Biol, 5, 917-923.
PDB code: 1bui
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.