| Structural highlights
1c78 is a 2 chain structure with sequence from Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 1c76, 1c77, 1c79 |
| Activity: | Aureolysin, with EC number 3.4.24.29 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Crystal structure of a staphylokinase: variant a model for reduced antigenicity.,Chen Y, Song G, Jiang F, Feng L, Zhang X, Ding Y, Bartlam M, Yang A, Ma X, Ye S, Liu Y, Tang H, Song H, Rao Z Eur J Biochem. 2002 Jan;269(2):705-11. PMID:11856331[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chen Y, Song G, Jiang F, Feng L, Zhang X, Ding Y, Bartlam M, Yang A, Ma X, Ye S, Liu Y, Tang H, Song H, Rao Z. Crystal structure of a staphylokinase: variant a model for reduced antigenicity. Eur J Biochem. 2002 Jan;269(2):705-11. PMID:11856331
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