View source for 2uzj


==Crystal structure of the mature streptococcal cysteine protease, mSpeB==
<StructureSection load='2uzj' size='340' side='right'caption='[[2uzj]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2uzj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pyogenes Streptococcus pyogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UZJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UZJ 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]] 1.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E64:N-[N-[1-HYDROXYCARBOXYETHYL-CARBONYL]LEUCYLAMINO-BUTYL]-GUANIDINE'>E64</scene></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=2uzj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uzj OCA], [https://pdbe.org/2uzj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uzj RCSB], [https://www.ebi.ac.uk/pdbsum/2uzj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uzj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SPEB_STRPY SPEB_STRPY] Important streptococcal virulence factor which cleaves human fibronectin and degrades vitronectin. Also cleaves human IL1B precursor to form biologically active IL1B. Can induce apoptosis in human monocytes and epithelial cells in vitro, and reduces phagocytic activity in monocytic cells. Thus, may play a role in bacterial colonization, invasion, and inhibition of wound healing.<ref>PMID:9864206</ref> 
== 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/uz/2uzj_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2uzj ConSurf].
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<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Invasive infections of Streptococcus pyogenes are dependent on the cysteine protease streptococcal pyrogenic exotoxin B. Previous structures of the enzyme have not disclosed the proper active-site configuration. Here, the crystal structure of the mature enzyme is presented to 1.55 A, disclosing a homodimer. A serine from one subunit inserts into the active site of the other to donate to the oxyanion hole and coordinates the ligand proximal to the active-site cysteine. Dimerization is unique to the mature form and is clearly a prerequisite for catalysis. The present structure supports a tripartite switch system that is triggered upon dimerization and substrate binding: (1) liberation of the active-site histidine from an inactive configuration, (2) relocation of residues blocking the substrate binding pockets and (3) repositioning of two active-site tryptophans to settle in the active configuration. Based on the present structure, the active site of clan CA cysteine proteases is expanded and a detailed mechanism of the deacylation mechanism is proposed. The results may have applications for the development of protease inhibitors specific to bacterial cysteine proteases.

Structure of the mature Streptococcal cysteine protease exotoxin mSpeB in its active dimeric form.,Olsen JG, Dagil R, Niclasen LM, Sorensen OE, Kragelund BB J Mol Biol. 2009 Oct 30;393(3):693-703. Epub 2009 Aug 25. PMID:19712682<ref>PMID:19712682</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2uzj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Exotoxin 3D structures|Exotoxin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptococcus pyogenes]]
[[Category: Dagil R]]
[[Category: Kragelund BB]]
[[Category: Niclasen LM]]
[[Category: Olsen JG]]
[[Category: Soerensen OE]]