spacer
spacer
Go to PDB code: 
protein ligands links
Hydrolase(serine protease) PDB id
2pk4
Jmol
Contents
Protein chain
80 a.a. *
Ligands
ACA
Waters ×106
* Residue conservation analysis
PDB id:
2pk4
Name: Hydrolase(serine protease)
Title: The refined structure of the epsilon-aminocaproic acid complex of human plasminogen kringle
Structure: Human plasminogen kringle 4. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
2.25Å     R-factor:   0.148    
Authors: A.Tulinsky,T.-P.Wu
Key ref:
T.P.Wu et al. (1991). The refined structure of the epsilon-aminocaproic acid complex of human plasminogen kringle 4. Biochemistry, 30, 10589-10594. PubMed id: 1657149 DOI: 10.1021/bi00107a030
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.
80 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/bi00107a030 Biochemistry 30:10589-10594 (1991)
PubMed id: 1657149  
 
 
The refined structure of the epsilon-aminocaproic acid complex of human plasminogen kringle 4.
T.P.Wu, K.Padmanabhan, A.Tulinsky, A.M.Mulichak.
 
  ABSTRACT  
 
The crystallographic structure of the plasminogen kringle 4-epsilon-aminocaproic acid (ACA) complex (K4-ACA) has been solved by molecular replacement rotation-translation methods utilizing the refined apo-K4 structure as a search model (Mulichak et al., 1991), and it has been refined to an R value of 0.148 at 2.25-A resolution. The K4-ACA structure consists of two interkringle residues, the kringle along with the ACA ligand, and 106 water molecules. The lysine-binding site has been confirmed to be a relatively open and shallow depression, lined by aromatic rings of Trp62, Phe64, and Trp72, which provide a highly nonpolar environment between doubly charged anionic and cationic centers formed by Asp55/Asp57 and Lys35/Arg71. A zwitterionic ACA ligand molecule is held by hydrogen-bonded ion pair interactions and van der Waals contacts between the charged centers. The lysine-binding site of apo-K4 and K4-ACA have been compared: the rms differences in main-chain and side-chain positions are 0.25 and 0.69 A, respectively, both practically within error of the determinations. The largest deviations in the binding site are due to different crystal packing interactions. Thus, the lysine-binding site appears to be preformed, and lysine binding does not require conformational changes of the host. The results of NMR studies of lysine binding with K4 are correlated with the structure of K4-ACA and agree well.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
19126539 K.Nogami, K.Nishiya, E.L.Saenko, M.Takeyama, K.Ogiwara, A.Yoshioka, and M.Shima (2009).
Identification of Plasmin-interactive Sites in the Light Chain of Factor VIII Responsible for Proteolytic Cleavage at Lys36.
  J Biol Chem, 284, 6934-6945.  
  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.  
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.  
15017359 M.L.Koschinsky, and S.M.Marcovina (2004).
Structure-function relationships in apolipoprotein(a): insights into lipoprotein(a) assembly and pathogenicity.
  Curr Opin Lipidol, 15, 167-174.  
11928826 E.Anglés-Cano, and G.Rojas (2002).
Apolipoprotein(a): structure-function relationship at the lysine-binding site and plasminogen activator cleavage site.
  Biol Chem, 383, 93-99.  
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.  
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.  
11567102 O.A.Ozhogina, M.Trexler, L.Bányai, M.Llinás, and L.Patthy (2001).
Origin of fibronectin type II (FN2) modules: structural analyses of distantly-related members of the kringle family idey the kringle domain of neurotrypsin as a potential link between FN2 domains and kringles.
  Protein Sci, 10, 2114-2122.  
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.  
  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.  
9649309 S.Xu (1998).
Apolipoprotein(a) binds to low-density lipoprotein at two distant sites in lipoprotein(a).
  Biochemistry, 37, 9284-9294.  
9585533 X.Chenivesse, T.Huby, J.Wickins, J.Chapman, and J.Thillet (1998).
Molecular cloning of the cDNA encoding the carboxy-terminal domain of chimpanzee apolipoprotein(a): an Asp57 --> Asn mutation in kringle IV-10 is associated with poor fibrin binding.
  Biochemistry, 37, 7213-7223.  
9521645 Y.Chang, I.Mochalkin, S.G.McCance, B.Cheng, A.Tulinsky, and F.J.Castellino (1998).
Structure and ligand binding determinants of the recombinant kringle 5 domain of human plasminogen.
  Biochemistry, 37, 3258-3271.
PDB code: 5hpg
  9385634 A.Hermann, W.R.Laws, and P.C.Harpel (1997).
Oxidation of apolipoprotein(a) inhibits kringle-associated lysine binding: the loss of intrinsic protein fluorescence suggests a role for tryptophan residues in the lysine binding site.
  Protein Sci, 6, 2324-2335.  
9305949 D.N.Marti, C.K.Hu, S.S.An, P.von Haller, J.Schaller, and M.Llinás (1997).
Ligand preferences of kringle 2 and homologous domains of human plasminogen: canvassing weak, intermediate, and high-affinity binding sites by 1H-NMR.
  Biochemistry, 36, 11591-11604.  
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.  
9295301 S.P.McCormick, J.K.Ng, C.M.Cham, S.Taylor, S.M.Marcovina, J.P.Segrest, R.E.Hammer, and S.G.Young (1997).
Transgenic mice expressing human ApoB95 and ApoB97. Evidence that sequences within the carboxyl-terminal portion of human apoB100 are important for the assembly of lipoprotein.
  J Biol Chem, 272, 23616-23622.  
8611560 I.I.Mathews, P.Vanderhoff-Hanaver, F.J.Castellino, and A.Tulinsky (1996).
Crystal structures of the recombinant kringle 1 domain of human plasminogen in complexes with the ligands epsilon-aminocaproic acid and trans-4-(aminomethyl)cyclohexane-1-carboxylic Acid.
  Biochemistry, 35, 2567-2576.
PDB codes: 1cea 1ceb
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.  
  8976552 R.A.Laskowski, N.M.Luscombe, M.B.Swindells, and J.M.Thornton (1996).
Protein clefts in molecular recognition and function.
  Protein Sci, 5, 2438-2452.  
8652577 S.Söhndel, C.K.Hu, D.Marti, M.Affolter, J.Schaller, M.Llinás, and E.E.Rickli (1996).
Recombinant gene expression and 1H NMR characteristics of the kringle (2 + 3) supermodule: spectroscopic/functional individuality of plasminogen kringle domains.
  Biochemistry, 35, 2357-2364.  
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.  
7592597 R.M.Lawn, N.W.Boonmark, K.Schwartz, G.E.Lindahl, D.P.Wade, C.D.Byrne, K.J.Fong, K.Meer, and L.Patthy (1995).
The recurring evolution of lipoprotein(a). Insights from cloning of hedgehog apolipoprotein(a).
  J Biol Chem, 270, 24004-24009.  
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.  
  8069221 K.Padmanabhan, T.P.Wu, K.G.Ravichandran, and A.Tulinsky (1994).
Kringle-kringle interactions in multimer kringle structures.
  Protein Sci, 3, 898-910.
PDB codes: 1pmk 1pml
  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
  7860098 W.R.Church, T.L.Messier, L.A.Ouellette, and S.E.Potts (1994).
A kringle-specific monoclonal antibody.
  Hybridoma, 13, 423-429.  
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 code is shown on the right.