1c79: Difference between revisions

Revision as of 13:03, 21 February 2008

STAPHYLOKINASE (SAK) DIMER

OverviewOverview

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.

About this StructureAbout this Structure

1C79 is a Single protein structure of sequence from Staphylococcus aureus. Active as Aureolysin, with EC number 3.4.24.29 Full crystallographic information is available from OCA.

ReferenceReference

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

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OCA

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-[[Image:1c79.gif|left|200px]]<br /><applet load="1c79" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1c79.gif|left|200px]]<br /><applet load="1c79" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1c79, resolution 2.3&Aring;" />
 '''STAPHYLOKINASE (SAK) DIMER'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-C79 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Active as [http://en.wikipedia.org/wiki/Aureolysin Aureolysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.29 3.4.24.29] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1C79 OCA].
+C79 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Active as [http://en.wikipedia.org/wiki/Aureolysin Aureolysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.29 3.4.24.29] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C79 OCA].
 ==Reference==
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 [[Category: beta-grasp family]]
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