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PDBsum entry 1c77

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protein Protein-protein interface(s) links
Hydrolase PDB id
1c77
Jmol
Contents
Protein chains
130 a.a. *
* Residue conservation analysis
PDB id:
1c77
Name: Hydrolase
Title: Staphylokinase (sak) dimer
Structure: Staphylokinase. Chain: a, b. Synonym: sak. Engineered: yes
Source: Staphylococcus aureus. Organism_taxid: 1280. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.30Å     R-factor:   0.198     R-free:   0.267
Authors: Z.Rao,F.Jiang,Y.Liu,X.Zhang,Y.Chen,M.Bartlam,H.Song,Y.Ding
Key ref:
Y.Chen et al. (2002). Crystal structure of a staphylokinase: variant a model for reduced antigenicity. Eur J Biochem, 269, 705-711. PubMed id: 11856331 DOI: 10.1046/j.0014-2956.2001.02706.x
Date:
01-Feb-00     Release date:   01-Aug-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P68802  (SAK_STAAU) -  Staphylokinase
Seq:
Struc:
163 a.a.
130 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     proteolysis   1 term 
  Biochemical function     serine-type endopeptidase activity     1 term  

 

 
DOI no: 10.1046/j.0014-2956.2001.02706.x Eur J Biochem 269:705-711 (2002)
PubMed id: 11856331  
 
 
Crystal structure of a staphylokinase: variant a model for reduced antigenicity.
Y.Chen, G.Song, F.Jiang, L.Feng, X.Zhang, Y.Ding, M.Bartlam, A.Yang, X.Ma, S.Ye, Y.Liu, H.Tang, H.Song, Z.Rao.
 
  ABSTRACT  
 
Staphylokinase (SAK) is a 15.5-kDa protein from Staphylococcus aureus that activates plasminogen by forming a 1 : 1 complex with plasmin. Recombinant SAK has been shown in clinical trials to induce fibrin-specific clot lysis in patients with acute myocardial infarction. However, SAK elicits high titers of neutralizing antibodies. Biochemical and protein engineering studies have demonstrated the feasibility of generating SAK variants with reduced antigenicity yet intact thrombolytic potency. Here, we present X-ray crystallographic evidence that the SAK(S41G) mutant may assume a dimeric structure. This dimer model, at 2.3-A resolution, could explain a major antigenic epitope (residues A72-F76 and residues K135-K136) located in the vicinity of the dimer interface as identified by phage-display. These results suggest that SAK antigenicity may be reduced by eliminating dimer formation. We propose several potential mutation sites at the dimer interface that may further reduce the antigenicity of SAK.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. Views of the salt bridge and hydrogen bonding networks (A) and the hydrophobic residues in the dimer interface (B). (A) Close up view of the salt bridge and hydrogen bonding networks in the dimer interface; more details are shown in Table 2 Go-. (B) The hydrophobic residues in the dimer interface. The figures are drawn with molscript[34] and rendered by raster3d[35].
Figure 4.
Fig. 4. The top view of the SAK dimer interface (A ) and mapping of residues involved in the antigenic sites and dimer interfaces (B). (A) The major antigenic area I (residues 72–76, and residues 135–136) in the close vicinity of the dimer interface is colored in red. The mapping ofresidues involved in the antigenic sites and dimer interfaces. (B) The dimer interface is shown by a dashed line. The mutated sites located in the dimer interface are colored in purple; the antigenic sites are colored in red, the other dimer interface residues in green. The figures are drawn with grasp[36].
 
  The above figures are reprinted by permission from the Federation of European Biochemical Societies: Eur J Biochem (2002, 269, 705-711) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20213046 J.He, R.Xu, X.Chen, K.Jia, X.Zhou, and K.Zhu (2010).
Simultaneous elimination of T- and B-cell epitope by structure-based mutagenesis of single Glu80 residue within recombinant staphylokinase.
  Acta Biochim Biophys Sin (Shanghai), 42, 209-215.  
18025559 R.Kochanowski, R.Kotlowski, and P.Szweda (2007).
Expression and intein-mediated purification of novel staphylokinase SakSTAR with reduced immunogenicity and antiplatelet and antithrombin activation.
  Appl Biochem Biotechnol, 141, 321-333.  
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