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PDBsum entry 1hpk

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Serine protease PDB id
1hpk
Jmol
Contents
Protein chain
79 a.a. *
Ligands
ACA
* Residue conservation analysis
PDB id:
1hpk
Name: Serine protease
Title: Solution nmr structure of the human plasminogen kringle 1 domain complexed with 6-aminohexanoic acid at ph 5.3, 310k, derived from randomly generated structures using simulated annealing, minimized average structure
Structure: Plasminogen. Chain: a. Fragment: kringle 1 domain. Other_details: contains the 6-aminohexanoic acid ligand
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: blood. Tissue: blood plasma
NMR struc: 1 models
Authors: M.Rejante,M.Llinas
Key ref: 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. PubMed id: 8181476
Date:
14-Aug-96     Release date:   12-Mar-97    
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.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     blood coagulation   2 terms 
  Biochemical function     calcium ion binding     2 terms  

 

 
Eur J Biochem 221:939-949 (1994)
PubMed id: 8181476  
 
 
Solution structure of the epsilon-aminohexanoic acid complex of human plasminogen kringle 1.
M.R.Rejante, M.Llinás.
 
  ABSTRACT  
 
The solution structure of the human plasminogen kringle 1 domain complexed to the antifibrinolytic drug 6-aminohexanoic acid (epsilon Ahx) was obtained on the basis of 1H-NMR spectroscopic data and dynamical simulated annealing calculations. Two sets of structures were derived starting from (a) random coil conformations and (b) the (mutated) crystallographic structure of the homologous prothrombin kringle 1. The two sets display essentially the same backbone folding (pairwise root-mean-square deviation, 0.15 nm) indicating that, regardless of the initial structure, the data is sufficient to locate a conformation corresponding to an essentially unique energy minimum. The conformations of residues connected to prolines were localized to energetically preferred regions of the Ramachandran map. The Pro30 peptide bond is proposed to be cis. The ligand-binding site of the kringle 1 is a shallow cavity composed of Pro33, Phe36, Trp62, Tyr64, Tyr72 and Tyr74. Doubly charged anionic and cationic centers configured by the side chains of Asp55 and Asp57, and Arg34 and Arg71, respectively, contribute to anchoring the zwitterionic epsilon Ahx molecule at the binding site. The ligand exhibits closer contacts with the kringle anionic centers (approximately 0.35 nm average O...H distance between the Asp55/Asp57 carboxylate and ligand amino groups) than with the cationic ones (approximately 0.52 nm closest O...H distances between the ligand carboxylate and the Arg34/Arg71 guanidino groups). The epsilon Ahx hydrocarbon chain rests flanked by Pro33, Tyr64, Tyr72 and Tyr74 on one side and Phe36 on the other. Dipolar (Overhauser) connectivities indicate that the ligand aliphatic moiety establishes close contacts with the Phe36 and Trp62 aromatic rings. The computed structure suggests that the epsilon Ahx molecule adopts a kinked conformation when complexed to kringle 1, effectively shortening its dipole length to approximately 0.65 nm.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20633357 G.A.Bermejo, and M.Llinás (2010).
Structure-oriented methods for protein NMR data analysis.
  Prog Nucl Magn Reson Spectrosc, 56, 311-328.  
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.  
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.  
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
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.  
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
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.  
  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.  
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
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.  
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
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.  
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.  
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.  
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.