View source for 6ggo


==Crystal structure of Salmonella zinc metalloprotease effector GtgA==
<StructureSection load='6ggo' size='340' side='right'caption='[[6ggo]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ggo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Typhimurium_str._14028S Salmonella enterica subsp. enterica serovar Typhimurium str. 14028S]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GGO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GGO 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6ggo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ggo OCA], [https://pdbe.org/6ggo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ggo RCSB], [https://www.ebi.ac.uk/pdbsum/6ggo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ggo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0F6AZI6_SALT1 A0A0F6AZI6_SALT1] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The closely related type III secretion system zinc metalloprotease effector proteins GtgA, GogA, and PipA are translocated into host cells during Salmonella infection. They then cleave nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) transcription factor subunits, dampening activation of the NF-kappaB signaling pathway and thereby suppressing host immune responses. We demonstrate here that GtgA, GogA, and PipA cleave a subset of NF-kappaB subunits including p65, RelB, and cRel but not NF-kappaB1 and NF-kappaB2, whereas the functionally similar type III secretion system effector NleC of enteropathogenic and enterohemorrhagic Escherichiacoli cleaved all five NF-kappaB subunits. Mutational analysis of NF-kappaB subunits revealed that a single nonconserved residue in NF-kappaB1 and NF-kappaB2 that corresponds to the P1' residue Arg-41 in p65, prevents cleavage of these subunits by GtgA, GogA, and PipA, explaining the observed substrate specificity of these enzymes. Crystal structures of GtgA in its apo form and in complex with the p65 N-terminal domain explained the importance of the P1' residue. Furthermore, the pattern of interactions suggested that GtgA recognizes NF-kappaB subunits by mimicking the shape and negative charge of the DNA phosphate backbone. Moreover, structure-based mutational analysis of GtgA uncovered amino acids that are required for the interaction of GtgA with p65, as well as those that are required for full activity of GtgA in suppressing NF-kappaB activation. This study therefore provides detailed and critical insight into the mechanism of substrate recognition by this family of proteins important for bacterial virulence.

Structure-function analyses of the bacterial zinc metalloprotease effector protein GtgA uncovers key residues required for deactivating NF-kappaB.,Jennings E, Esposito D, Rittinger K, Thurston TLM J Biol Chem. 2018 Jul 26. pii: RA118.004255. doi: 10.1074/jbc.RA118.004255. PMID:30049795<ref>PMID:30049795</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ggo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Salmonella enterica subsp. enterica serovar Typhimurium str. 14028S]]
[[Category: Esposito D]]
[[Category: Jennings E]]
[[Category: Rittinger K]]
[[Category: Thurston T]]