PDBsum entry 1bml

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Blood clotting PDB id
Protein chains
250 a.a. *
318 a.a. *
* Residue conservation analysis
PDB id:
Name: Blood clotting
Title: Complex of the catalytic domain of human plasmin and strepto
Structure: Plasmin. Chain: a, b. Fragment: catalytic domain. Engineered: yes. Mutation: yes. Streptokinase. Chain: c, d
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Streptococcus dysgalactiae subsp. Equi organism_taxid: 119602. Strain: subsp. Equisimilis
Biol. unit: Tetramer (from PQS)
2.90Å     R-factor:   0.201     R-free:   0.291
Authors: X.Wang,X.C.Zhang
Key ref:
X.Wang et al. (1998). Crystal structure of the catalytic domain of human plasmin complexed with streptokinase. Science, 281, 1662-1665. PubMed id: 9733510 DOI: 10.1126/science.281.5383.1662
25-May-99     Release date:   02-Aug-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P00747  (PLMN_HUMAN) -  Plasminogen
810 a.a.
250 a.a.*
Protein chains
Pfam   ArchSchema ?
P00779  (STRP_STREQ) -  Streptokinase C
440 a.a.
318 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B: 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!
  Cellular component     extracellular region   1 term 
  Biological process     pathogenesis   3 terms 
  Biochemical function     catalytic activity     2 terms  


DOI no: 10.1126/science.281.5383.1662 Science 281:1662-1665 (1998)
PubMed id: 9733510  
Crystal structure of the catalytic domain of human plasmin complexed with streptokinase.
X.Wang, X.Lin, J.A.Loy, J.Tang, X.C.Zhang.
Streptokinase is a plasminogen activator widely used in treating blood-clotting disorders. Complexes of streptokinase with human plasminogen can hydrolytically activate other plasminogen molecules to plasmin, which then dissolves blood clots. A similar binding activation mechanism also occurs in some key steps of blood coagulation. The crystal structure of streptokinase complexed with the catalytic unit of human plasmin was solved at 2.9 angstroms. The amino-terminal domain of streptokinase in the complex is hypothesized to enhance the substrate recognition. The carboxyl-terminal domain of streptokinase, which binds near the activation loop of plasminogen, is likely responsible for the contact activation of plasminogen in the complex.
  Selected figure(s)  
Figure 1.
Fig. 1. Stereoview of the crystal structure of human µPm-SK complex in C[ ]traces. The µPm molecule is shown in blue with the NH[2]-terminal short peptide in dark blue. The , , and domains of SK are shown in yellow, green, and purple, respectively. The chymotrypsin equivalences of the labeled µPm residues are 15 (561 in Pm), 16 (562), 57 (603), 102 (646), and 195 (741).
Figure 2.
Fig. 2. Interactions between human µPm and the (A) and (B) domains of SK. µPm is shown in blue and SK in orange. The side chains involved in the interactions are also shown as stick models and labeled. Also labeled are the secondary structures in the SK and domains. Abbreviations for the amino acid residues are as follows: A, Ala; D, Asp; E, Glu; F, Phe; H, His; K, Lys; L, Leu; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
  The above figures are reprinted by permission from the AAAs: Science (1998, 281, 1662-1665) copyright 1998.  
  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.  
20637417 E.Eren, M.Murphy, J.Goguen, and B.van den Berg (2010).
An active site water network in the plasminogen activator pla from Yersinia pestis.
  Structure, 18, 809-818.
PDB codes: 2x4m 2x55 2x56
19737105 R.J.Olsen, and J.M.Musser (2010).
Molecular pathogenesis of necrotizing fasciitis.
  Annu Rev Pathol, 5, 1.  
20028034 R.N.Bohnsack, M.Patel, L.J.Olson, S.S.Twining, and N.M.Dahms (2010).
Residues essential for plasminogen binding by the cation-independent mannose 6-phosphate receptor.
  Biochemistry, 49, 635-644.  
20112045 S.S.Gerber, S.Lejon, M.Locher, and J.Schaller (2010).
The human alpha(2)-plasmin inhibitor: functional characterization of the unique plasmin(ogen)-binding region.
  Cell Mol Life Sci, 67, 1505-1518.  
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.  
19566545 I.Y.Sazonova, R.A.McNamee, A.K.Houng, S.M.King, L.Hedstrom, and G.L.Reed (2009).
Reprogrammed streptokinases develop fibrin-targeting and dissolve blood clots with more potency than tissue plasminogen activator.
  J Thromb Haemost, 7, 1321-1328.  
19790056 K.Ede, K.K.Hwang, C.C.Wu, M.Wu, Y.H.Yang, W.S.Lin, D.Chien, P.C.Chen, B.P.Tsao, D.K.McCurdy, and P.P.Chen (2009).
Plasmin immunization preferentially induces potentially prothrombotic IgG anticardiolipin antibodies in MRL/MpJ mice.
  Arthritis Rheum, 60, 3108-3117.  
19801674 R.Aneja, M.Datt, B.Singh, S.Kumar, and G.Sahni (2009).
Identification of a new exosite involved in catalytic turnover by the streptokinase-plasmin activator complex during human plasminogen activation.
  J Biol Chem, 284, 32642-32650.  
18658146 I.M.Verhamme, and P.E.Bock (2008).
Rapid-reaction kinetic characterization of the pathway of streptokinase-plasmin catalytic complex formation.
  J Biol Chem, 283, 26137-26147.  
17111203 A.Kunamneni, T.T.Abdelghani, and P.Ellaiah (2007).
Streptokinase--the drug of choice for thrombolytic therapy.
  J Thromb Thrombolysis, 23, 9.  
17635705 J.L.Degen, T.H.Bugge, and J.D.Goguen (2007).
Fibrin and fibrinolysis in infection and host defense.
  J Thromb Haemost, 5, 24-31.  
17469158 W.S.Lin, P.C.Chen, C.D.Yang, E.Cho, B.H.Hahn, J.Grossman, K.K.Hwang, and P.P.Chen (2007).
Some antiphospholipid antibodies recognize conformational epitopes shared by beta2-glycoprotein I and the homologous catalytic domains of several serine proteases.
  Arthritis Rheum, 56, 1638-1647.  
16827654 L.I.Sokolovskaya, A.Y.Slominskii, and G.L.Volkov (2006).
Induction of catalytic activity of plasminogen by monoclonal antibody IV-Ic in the presence of divalent metal cations and alpha2-antiplasmin.
  Biochemistry (Mosc), 71, 627-633.  
16857686 P.Panizzi, P.D.Boxrud, I.M.Verhamme, and P.E.Bock (2006).
Binding of the COOH-terminal lysine residue of streptokinase to plasmin(ogen) kringles enhances formation of the streptokinase.plasmin(ogen) catalytic complexes.
  J Biol Chem, 281, 26774-26778.  
16230340 P.Panizzi, R.Friedrich, P.Fuentes-Prior, H.K.Kroh, J.Briggs, G.Tans, W.Bode, and P.E.Bock (2006).
Novel fluorescent prothrombin analogs as probes of staphylocoagulase-prothrombin interactions.
  J Biol Chem, 281, 1169-1178.  
16230338 R.Friedrich, P.Panizzi, S.Kawabata, W.Bode, P.E.Bock, and P.Fuentes-Prior (2006).
Structural basis for reduced staphylocoagulase-mediated bovine prothrombin activation.
  J Biol Chem, 281, 1188-1195.
PDB code: 2a1d
  17114499 Y.H.Yang, K.K.Hwang, J.FitzGerald, J.M.Grossman, M.Taylor, B.H.Hahn, and P.P.Chen (2006).
Antibodies against the activated coagulation factor X (FXa) in the antiphospholipid syndrome that interfere with the FXa inactivation by antithrombin.
  J Immunol, 177, 8219-8225.  
16320350 C.S.Lu, A.A.Horizon, K.K.Hwang, J.FitzGerald, W.S.Lin, B.H.Hahn, D.J.Wallace, A.L.Metzger, M.H.Weisman, and P.P.Chen (2005).
Identification of polyclonal and monoclonal antibodies against tissue plasminogen activator in the antiphospholipid syndrome.
  Arthritis Rheum, 52, 4018-4027.  
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
15623524 R.R.Bean, I.M.Verhamme, and P.E.Bock (2005).
Role of the streptokinase alpha-domain in the interactions of streptokinase with plasminogen and plasmin.
  J Biol Chem, 280, 7504-7510.  
15972548 S.Lizano, and K.H.Johnston (2005).
Structural diversity of streptokinase and activation of human plasminogen.
  Infect Immun, 73, 4451-4453.  
15892855 W.Bode (2005).
The structure of thrombin, a chameleon-like proteinase.
  J Thromb Haemost, 3, 2379-2388.  
14679231 A.Kalia, and D.E.Bessen (2004).
Natural selection and evolution of streptococcal virulence genes involved in tissue-specific adaptations.
  J Bacteriol, 186, 110-121.  
15558209 P.Panizzi, R.Friedrich, P.Fuentes-Prior, W.Bode, and P.E.Bock (2004).
The staphylocoagulase family of zymogen activator and adhesion proteins.
  Cell Mol Life Sci, 61, 2793-2798.  
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
12878727 I.P.Gladysheva, R.B.Turner, I.Y.Sazonova, L.Liu, and G.L.Reed (2003).
Coevolutionary patterns in plasminogen activation.
  Proc Natl Acad Sci U S A, 100, 9168-9172.  
  12877576 L.Guinn, J.Johnson, and V.M.Doctor (2003).
Ionic modulation of the effects of heparin and 6-aminohexanoic acid on plasminogen activation by streptokinase: the role of ionic strength, divalent cations and chloride.
  Eur J Drug Metab Pharmacokinet, 28, 161-166.  
14523451 R.Friedrich, P.Panizzi, P.Fuentes-Prior, K.Richter, I.Verhamme, P.J.Anderson, S.Kawabata, R.Huber, W.Bode, and P.E.Bock (2003).
Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation.
  Nature, 425, 535-539.
PDB codes: 1nu7 1nu9
12180989 A.I.Azuaga, C.M.Dobson, P.L.Mateo, and F.Conejero-Lara (2002).
Unfolding and aggregation during the thermal denaturation of streptokinase.
  Eur J Biochem, 269, 4121-4133.  
12065504 K.Steiner, and H.Malke (2002).
Dual control of streptokinase and streptolysin S production by the covRS and fasCAX two-component regulators in Streptococcus dysgalactiae subsp. equisimilis.
  Infect Immun, 70, 3627-3636.  
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
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.  
11462234 S.Masmoudi, S.E.Antonarakis, T.Schwede, A.M.Ghorbel, M.Gratri, M.P.Pappasavas, M.Drira, A.Elgaied-Boulila, M.Wattenhofer, C.Rossier, H.S.Scott, H.Ayadi, and M.Guipponi (2001).
Novel missense mutations of TMPRSS3 in two consanguineous Tunisian families with non-syndromic autosomal recessive deafness.
  Hum Mutat, 18, 101-108.  
10637221 H.Jing, Y.Xu, M.Carson, D.Moore, K.J.Macon, J.E.Volanakis, and S.V.Narayana (2000).
New structural motifs on the chymotrypsin fold and their potential roles in complement factor B.
  EMBO J, 19, 164-173.
PDB code: 1dle
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.  
10828958 L.B.Johnsen, L.K.Rasmussen, T.E.Petersen, M.Etzerodt, and S.N.Fedosov (2000).
Kinetic and structural characterization of a two-domain streptokinase: dissection of domain functionality.
  Biochemistry, 39, 6440-6448.  
11076540 P.D.Boxrud, and P.E.Bock (2000).
Streptokinase binds preferentially to the extended conformation of plasminogen through lysine binding site and catalytic domain interactions.
  Biochemistry, 39, 13974-13981.  
10866798 S.Wang, G.L.Reed, and L.Hedstrom (2000).
Zymogen activation in the streptokinase-plasminogen complex. Ile1 is required for the formation of a functional active site.
  Eur J Biochem, 267, 3994-4001.  
11092938 Y.Tang, J.Zhang, L.Gui, C.Wu, R.Fan, W.Chang, and D.Liang (2000).
Crystallization and preliminary X-ray analysis of earthworm fibrinolytic enzyme component A from Eisenia fetida.
  Acta Crystallogr D Biol Crystallogr, 56, 1659-1661.  
  10631997 A.Chaudhary, S.Vasudha, K.Rajagopal, S.S.Komath, N.Garg, M.Yadav, S.C.Mande, and G.Sahni (1999).
Function of the central domain of streptokinase in substrate plasminogen docking and processing revealed by site-directed mutagenesis.
  Protein Sci, 8, 2791-2805.  
  10048340 A.I.Azuaga, N.D.Woodruff, F.Conejero-Lara, V.F.Cox, R.A.Smith, and C.M.Dobson (1999).
Expression and characterization of the intact N-terminal domain of streptokinase.
  Protein Sci, 8, 443-446.  
10430864 G.L.Reed, A.K.Houng, L.Liu, B.Parhami-Seren, L.H.Matsueda, S.Wang, and L.Hedstrom (1999).
A catalytic switch and the conversion of streptokinase to a fibrin-targeted plasminogen activator.
  Proc Natl Acad Sci U S A, 96, 8879-8883.  
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.  
10052945 J.Shobe, C.D.Dickinson, and W.Ruf (1999).
Regulation of the catalytic function of coagulation factor VIIa by a conformational linkage of surface residue Glu 154 to the active site.
  Biochemistry, 38, 2745-2751.  
10467148 K.P.Hopfner, A.Lang, A.Karcher, K.Sichler, E.Kopetzki, H.Brandstetter, R.Huber, W.Bode, and R.A.Engh (1999).
Coagulation factor IXa: the relaxed conformation of Tyr99 blocks substrate binding.
  Structure, 7, 989-996.
PDB code: 1rfn
  10024545 L.B.Johnsen, K.Poulsen, M.Kilian, and T.E.Petersen (1999).
Purification and cloning of a streptokinase from Streptococcus uberis.
  Infect Immun, 67, 1072-1078.  
10213631 S.Wang, G.L.Reed, and L.Hedstrom (1999).
Deletion of Ile1 changes the mechanism of streptokinase: evidence for the molecular sexuality hypothesis.
  Biochemistry, 38, 5232-5240.  
9808033 C.T.Esmon, and T.Mather (1998).
Switching serine protease specificity.
  Nat Struct Biol, 5, 933-937.  
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 codes are shown on the right.