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<StructureSection load='1g4u' size='340' side='right'caption='[[1g4u]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='1g4u' size='340' side='right'caption='[[1g4u]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1g4u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ ] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G4U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1G4U FirstGlance]. <br>
<table><tr><td colspan='2'>[[1g4u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Typhimurium Salmonella enterica subsp. enterica serovar Typhimurium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G4U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1G4U FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1g4w|1g4w]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAC1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1g4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g4u OCA], [https://pdbe.org/1g4u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1g4u RCSB], [https://www.ebi.ac.uk/pdbsum/1g4u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1g4u ProSAT]</span></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=1g4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g4u OCA], [https://pdbe.org/1g4u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1g4u RCSB], [https://www.ebi.ac.uk/pdbsum/1g4u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1g4u ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/SPTP_SALTY SPTP_SALTY]] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein includes tyrosine phosphatase and GTPase activating protein (GAP) activities. After bacterial internalization, GAP mediates the reversal of the cytoskeletal changes induced by SopE. This function is independent of its tyrosine phosphatase activity, which remains unclear.<ref>PMID:8866485</ref> <ref>PMID:10499590</ref> <ref>PMID:11163217</ref> [[https://www.uniprot.org/uniprot/RAC1_HUMAN RAC1_HUMAN]] Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. In glioma cells, promotes cell migration and invasion.<ref>PMID:1643658</ref> <ref>PMID:9121475</ref> <ref>PMID:19934221</ref> <ref>PMID:19403692</ref> <ref>PMID:20696765</ref>  Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction.<ref>PMID:1643658</ref> <ref>PMID:9121475</ref> <ref>PMID:19934221</ref> <ref>PMID:19403692</ref> <ref>PMID:20696765</ref> 
[https://www.uniprot.org/uniprot/SPTP_SALTY SPTP_SALTY] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein includes tyrosine phosphatase and GTPase activating protein (GAP) activities. After bacterial internalization, GAP mediates the reversal of the cytoskeletal changes induced by SopE. This function is independent of its tyrosine phosphatase activity, which remains unclear.<ref>PMID:8866485</ref> <ref>PMID:10499590</ref> <ref>PMID:11163217</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=1g4u 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=1g4u ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Salmonella spp. utilize a specialized protein secretion system to deliver a battery of effector proteins into host cells. Several of these effectors stimulate Cdc42- and Rac1-dependent cytoskeletal changes that promote bacterial internalization. These potentially cytotoxic alterations are rapidly reversed by the effector SptP, a tyrosine phosphatase and GTPase activating protein (GAP) that targets Cdc42 and Rac1. The 2.3 A resolution crystal structure of an SptP-Rac1 transition state complex reveals an unusual GAP architecture that mimics host functional homologs. The phosphatase domain possesses a conserved active site but distinct surface properties. Binding to Rac1 induces a dramatic stabilization in SptP of a four-helix bundle that makes extensive contacts with the Switch I and Switch II regions of the GTPase.
Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1.,Stebbins CE, Galan JE Mol Cell. 2000 Dec;6(6):1449-60. PMID:11163217<ref>PMID:11163217</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1g4u" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Galan, J E]]
[[Category: Salmonella enterica subsp. enterica serovar Typhimurium]]
[[Category: Stebbins, C E]]
[[Category: Galan JE]]
[[Category: 4-helix bundle]]
[[Category: Stebbins CE]]
[[Category: Gap]]
[[Category: Gtpase]]
[[Category: Signaling protein]]
[[Category: Tyrosine phosphatase]]
[[Category: Virulence factor]]

Revision as of 07:22, 7 February 2024

CRYSTAL STRUCTURE OF THE SALMONELLA TYROSINE PHOSPHATASE AND GTPASE ACTIVATING PROTEIN SPTP BOUND TO RAC1

1g4u, resolution 2.30Å

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