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==Solution structure of the Wiskott-Aldrich Syndrome Protein (WASP) autoinhibited core domain complexed with (S)-wiskostatin, a small molecule inhibitor==
==Solution structure of the Wiskott-Aldrich Syndrome Protein (WASP) autoinhibited core domain complexed with (S)-wiskostatin, a small molecule inhibitor==
<StructureSection load='1t84' size='340' side='right' caption='[[1t84]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
<StructureSection load='1t84' size='340' side='right'caption='[[1t84]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1t84]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T84 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T84 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1t84]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T84 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T84 FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=WSK:(2S)-1-(3,6-DIBROMO-9H-CARBAZOL-9-YL)-3-(DIMETHYLAMINO)PROPAN-2-OL'>WSK</scene><br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ej5|1ej5]], [[1cee|1cee]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=WSK:(2S)-1-(3,6-DIBROMO-9H-CARBAZOL-9-YL)-3-(DIMETHYLAMINO)PROPAN-2-OL'>WSK</scene></td></tr>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">WASP (residues 242-310 and 461-492) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=1t84 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t84 OCA], [https://pdbe.org/1t84 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t84 RCSB], [https://www.ebi.ac.uk/pdbsum/1t84 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t84 ProSAT]</span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t84 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t84 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t84 RCSB], [http://www.ebi.ac.uk/pdbsum/1t84 PDBsum]</span></td></tr>
</table>
<table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/WASP_HUMAN WASP_HUMAN]] Defects in WAS are the cause of Wiskott-Aldrich syndrome (WAS) [MIM:[http://omim.org/entry/301000 301000]]; also known as eczema-thrombocytopenia-immunodeficiency syndrome. WAS is an X-linked recessive immunodeficiency characterized by eczema, thrombocytopenia, recurrent infections, and bloody diarrhea. Death usually occurs before age 10.<ref>PMID:7753869</ref> <ref>PMID:8528198</ref> <ref>PMID:8528199</ref> <ref>PMID:8682510</ref> <ref>PMID:9126958</ref> <ref>PMID:9098856</ref> <ref>PMID:9683546</ref> <ref>PMID:9713366</ref> <ref>PMID:9445409</ref> <ref>PMID:10447259</ref> <ref>PMID:11793485</ref>  Defects in WAS are the cause of thrombocytopenia type 1 (THC1) [MIM:[http://omim.org/entry/313900 313900]]. Thrombocytopenia is defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting.<ref>PMID:8528199</ref> <ref>PMID:10447259</ref> <ref>PMID:7795648</ref> <ref>PMID:11167787</ref> <ref>PMID:11877312</ref>  Defects in WAS are a cause of neutropenia severe congenital X-linked (XLN) [MIM:[http://omim.org/entry/300299 300299]]. XLN is an immunodeficiency syndrome characterized by recurrent major bacterial infections, severe congenital neutropenia, and monocytopenia.<ref>PMID:11242115</ref>
[https://www.uniprot.org/uniprot/WASP_HUMAN WASP_HUMAN] Defects in WAS are the cause of Wiskott-Aldrich syndrome (WAS) [MIM:[https://omim.org/entry/301000 301000]; also known as eczema-thrombocytopenia-immunodeficiency syndrome. WAS is an X-linked recessive immunodeficiency characterized by eczema, thrombocytopenia, recurrent infections, and bloody diarrhea. Death usually occurs before age 10.<ref>PMID:7753869</ref> <ref>PMID:8528198</ref> <ref>PMID:8528199</ref> <ref>PMID:8682510</ref> <ref>PMID:9126958</ref> <ref>PMID:9098856</ref> <ref>PMID:9683546</ref> <ref>PMID:9713366</ref> <ref>PMID:9445409</ref> <ref>PMID:10447259</ref> <ref>PMID:11793485</ref>  Defects in WAS are the cause of thrombocytopenia type 1 (THC1) [MIM:[https://omim.org/entry/313900 313900]. Thrombocytopenia is defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting.<ref>PMID:8528199</ref> <ref>PMID:10447259</ref> <ref>PMID:7795648</ref> <ref>PMID:11167787</ref> <ref>PMID:11877312</ref>  Defects in WAS are a cause of neutropenia severe congenital X-linked (XLN) [MIM:[https://omim.org/entry/300299 300299]. XLN is an immunodeficiency syndrome characterized by recurrent major bacterial infections, severe congenital neutropenia, and monocytopenia.<ref>PMID:11242115</ref>  
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/WASP_HUMAN WASP_HUMAN]] Effector protein for Rho-type GTPases. Regulates actin filament reorganization via its interaction with the Arp2/3 complex. Important for efficient actin polymerization. Possible regulator of lymphocyte and platelet function. Mediates actin filament reorganization and the formation of actin pedestals upon infection by pathogenic bacteria.<ref>PMID:12235133</ref> <ref>PMID:16275905</ref> <ref>PMID:18650809</ref>
[https://www.uniprot.org/uniprot/WASP_HUMAN WASP_HUMAN] Effector protein for Rho-type GTPases. Regulates actin filament reorganization via its interaction with the Arp2/3 complex. Important for efficient actin polymerization. Possible regulator of lymphocyte and platelet function. Mediates actin filament reorganization and the formation of actin pedestals upon infection by pathogenic bacteria.<ref>PMID:12235133</ref> <ref>PMID:16275905</ref> <ref>PMID:18650809</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t8/1t84_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t8/1t84_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </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/chain_selection.php?pdb_ID=2ata ConSurf].
</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=1t84 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 1t84" style="background-color:#fffaf0;"></div>
==See Also==
*[[Wiskott-Aldrich syndrome protein 3D structures|Wiskott-Aldrich syndrome protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Bickford, L C.]]
[[Category: Large Structures]]
[[Category: Kim, A S.]]
[[Category: Bickford LC]]
[[Category: Kirschner, M W.]]
[[Category: Kim AS]]
[[Category: Morgan, D.]]
[[Category: Kirschner MW]]
[[Category: Ouerfelli, O.]]
[[Category: Morgan D]]
[[Category: Peterson, J R.]]
[[Category: Ouerfelli O]]
[[Category: Rosen, M K.]]
[[Category: Peterson JR]]
[[Category: Alpha helix]]
[[Category: Rosen MK]]
[[Category: Beta-hairpin turn]]
[[Category: Signaling protein]]