spacer
spacer

PDBsum entry 1ddj

Go to PDB code: 
protein Protein-protein interface(s) links
Blood clotting PDB id
1ddj
Jmol
Contents
Protein chain
247 a.a. *
Waters ×741
* Residue conservation analysis
PDB id:
1ddj
Name: Blood clotting
Title: Crystal structure of human plasminogen catalytic domain
Structure: Plasminogen. Chain: a, b, c, d. Fragment: catalytic domain. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: blood. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.00Å     R-factor:   0.194     R-free:   0.267
Authors: X.Wang,S.Terzyan,J.Tang,J.Loy,X.Lin,X.Zhang
Key ref:
X.Wang et al. (2000). Human plasminogen catalytic domain undergoes an unusual conformational change upon activation. J Mol Biol, 295, 903-914. PubMed id: 10656799 DOI: 10.1006/jmbi.1999.3397
Date:
10-Nov-99     Release date:   18-Feb-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00747  (PLMN_HUMAN) -  Plasminogen
Seq:
Struc:
 
Seq:
Struc:
810 a.a.
247 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.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     proteolysis   1 term 
  Biochemical function     catalytic activity     2 terms  

 

 
DOI no: 10.1006/jmbi.1999.3397 J Mol Biol 295:903-914 (2000)
PubMed id: 10656799  
 
 
Human plasminogen catalytic domain undergoes an unusual conformational change upon activation.
X.Wang, S.Terzyan, J.Tang, J.A.Loy, X.Lin, X.C.Zhang.
 
  ABSTRACT  
 
Activation of the serine protease plasmin from its zymogen, plasminogen, is the key step in fibrinolysis leading to blood clot dissolution. It also plays critical roles in cell migration, such as in tumor metastasis. Here, we report the crystal structure of an inactive S741A mutant of human plasminogen catalytic domain at 2.0 A resolution. This structure permits a direct comparison with that of the plasmin catalytic unit. Unique conformational differences are present between these two structures that are not seen in other zymogen-enzyme pairs of the trypsin family. The functional significance of these differences and the structural basis of plasminogen activation is discussed in the light of this new structure.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Structural deviation between µPlg and µPm along the peptide chain. Each pair of µPlg (using all four molecules of the asymmetric unit) and µPm was optimally superimposed using vert, similar 180 C^a atom pairs with a 1.0 Å distance cutoff. The red lines are the minimum rms deviation. The blue lines extended from the red lines are the maximum, serving to indicate the conformational rigidity/flexibility among the four µPlg molecules. The graph above the horizontal axis shows the main-chain atom rms deviation, and that below the axis is the corresponding side-chain deviation. The inset is a similar plot of chymotrypsinogen against chymotrypsin. The regions of significantly smaller conformational changes in chymotrypsinogen activation than in plasminogen activation are marked with arrows.
Figure 5.
Figure 5. Structural comparison of µPlg with µPm. (a) The activation loop region. The C^a trace of µPlg is in magenta, and the side-chains are in red except the disulfide bond Cys558-Cys566 which is in yellow. The backbone and residue side-chains of µPm are in light and dark blue, respectively. The backbone of the flexible autolysis loop is shown as a curved model. Residues 559 (14), 561 (15), 562 (16), 566 (20), 685 (141), 698 (156), 735 (189) and 740 (194) are labeled. (b) The active-site region. Color codes are the same as above. The superimposition shows that µPm has a well defined S[1] specificity pocket and oxyanion hole, while in µPlg, the components of the active site apparatus are distorted and clearly non-functional. Residues 562 (16), 586 (40), 603 (57), 646 (102), 735 (189), 738 (192), 740 (194), 741 (195), 761 (215) and 765 (219) are labeled.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 295, 903-914) copyright 2000.  
  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.  
19593387 J.A.Kornblatt (2009).
Reduction of canine plasminogen leads to an expanded molecule which precipitates.
  PLoS One, 4, e6196.  
19111067 R.R.Thangudu, M.Manoharan, N.Srinivasan, F.Cadet, R.Sowdhamini, and B.Offmann (2008).
Analysis on conservation of disulphide bonds and their structural features in homologous protein domain families.
  BMC Struct Biol, 8, 55.  
17002656 V.M.Chen, and P.J.Hogg (2006).
Allosteric disulfide bonds in thrombosis and thrombolysis.
  J Thromb Haemost, 4, 2533-2541.  
16279944 F.Carafoli, D.Y.Chirgadze, T.L.Blundell, and E.Gherardi (2005).
Crystal structure of the beta-chain of human hepatocyte growth factor-like/macrophage stimulating protein.
  FEBS J, 272, 5799-5807.
PDB code: 2asu
15211511 S.Terzyan, N.Wakeham, P.Zhai, K.Rodgers, and X.C.Zhang (2004).
Characterization of Lys-698-to-Met substitution in human plasminogen catalytic domain.
  Proteins, 56, 277-284.
PDB code: 1rjx
12773528 V.Sundram, J.S.Nanda, K.Rajagopal, J.Dhar, A.Chaudhary, and G.Sahni (2003).
Domain truncation studies reveal that the streptokinase-plasmin activator complex utilizes long range protein-protein interactions with macromolecular substrate to maximize catalytic turnover.
  J Biol Chem, 278, 30569-30577.  
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.  
11823416 M.Budayova-Spano, M.Lacroix, N.M.Thielens, G.J.Arlaud, J.C.Fontecilla-Camps, and C.Gaboriaud (2002).
The crystal structure of the zymogen catalytic domain of complement protease C1r reveals that a disruptive mechanical stress is required to trigger activation of the C1 complex.
  EMBO J, 21, 231-239.
PDB code: 1gpz
12429092 M.Budayova-Spano, W.Grabarse, N.M.Thielens, H.Hillen, M.Lacroix, M.Schmidt, J.C.Fontecilla-Camps, G.J.Arlaud, and C.Gaboriaud (2002).
Monomeric structures of the zymogen and active catalytic domain of complement protease c1r: further insights into the c1 activation mechanism.
  Structure, 10, 1509-1519.
PDB codes: 1md7 1md8
11470437 C.Eigenbrot, D.Kirchhofer, M.S.Dennis, L.Santell, R.A.Lazarus, J.Stamos, and M.H.Ultsch (2001).
The factor VII zymogen structure reveals reregistration of beta strands during activation.
  Structure, 9, 627-636.
PDB code: 1jbu
11502203 H.H.Petersen, M.Hansen, S.L.Schousboe, and P.A.Andreasen (2001).
Localization of epitopes for monoclonal antibodies to urokinase-type plasminogen activator: relationship between epitope localization and effects of antibodies on molecular interactions of the enzyme.
  Eur J Biochem, 268, 4430-4439.  
11742690 K.Lähteenmäki, P.Kuusela, and T.K.Korhonen (2001).
Bacterial plasminogen activators and receptors.
  FEMS Microbiol Rev, 25, 531-552.  
11168406 R.Egelund, T.E.Petersen, and P.A.Andreasen (2001).
A serpin-induced extensive proteolytic susceptibility of urokinase-type plasminogen activator implicates distortion of the proteinase substrate-binding pocket and oxyanion hole in the serpin inhibitory mechanism.
  Eur J Biochem, 268, 673-685.  
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.