1c78

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(New page: 200px<br /><applet load="1c78" size="450" color="white" frame="true" align="right" spinBox="true" caption="1c78, resolution 2.3&Aring;" /> '''STAPHYLOKINASE (SAK) ...)
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caption="1c78, resolution 2.3&Aring;" />
'''STAPHYLOKINASE (SAK) DIMER'''<br />
'''STAPHYLOKINASE (SAK) DIMER'''<br />
==Overview==
==Overview==
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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.
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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==
==About this Structure==
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1C78 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=1C78 OCA].
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1C78 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=1C78 OCA].
==Reference==
==Reference==
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[[Category: beta-grasp family]]
[[Category: beta-grasp family]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 12:13:45 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:03:08 2008''

Revision as of 10:03, 21 February 2008

Image:1c78.gif

1c78, resolution 2.3Å

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STAPHYLOKINASE (SAK) DIMER

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.

About this Structure

1C78 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.

Reference

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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