1c78: Difference between revisions
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==STAPHYLOKINASE (SAK) DIMER== | |||
<StructureSection load='1c78' size='340' side='right'caption='[[1c78]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1c78]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C78 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C78 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1c78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c78 OCA], [https://pdbe.org/1c78 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c78 RCSB], [https://www.ebi.ac.uk/pdbsum/1c78 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c78 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SAK_STAAU SAK_STAAU] Potent plasminogen activator that converts plasminogen into plasmin. It forms a 1:1 complex with plasmin, which in turn activates other plasminogen molecules. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c7/1c78_consurf.spt"</scriptWhenChecked> | |||
== | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1c78 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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. | 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<ref>PMID:11856331</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1c78" style="background-color:#fffaf0;"></div> | |||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
[[Category: Bartlam | [[Category: Bartlam M]] | ||
[[Category: Chen | [[Category: Chen Y]] | ||
[[Category: Ding | [[Category: Ding Y]] | ||
[[Category: Jiang | [[Category: Jiang F]] | ||
[[Category: Liu | [[Category: Liu Y]] | ||
[[Category: Rao | [[Category: Rao Z]] | ||
[[Category: Song | [[Category: Song H]] | ||
[[Category: Zhang | [[Category: Zhang X]] | ||
Latest revision as of 02:24, 28 December 2023
STAPHYLOKINASE (SAK) DIMERSTAPHYLOKINASE (SAK) DIMER
Structural highlights
FunctionSAK_STAAU Potent plasminogen activator that converts plasminogen into plasmin. It forms a 1:1 complex with plasmin, which in turn activates other plasminogen molecules. 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 PubMedStaphylokinase (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 |
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