View source for 7ski


==Pertussis toxin in complex with PJ34==
<StructureSection load='7ski' size='340' side='right'caption='[[7ski]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ski]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bordetella_pertussis Bordetella pertussis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SKI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SKI 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]] 1.0991244&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P34:N~2~,N~2~-DIMETHYL-N~1~-(6-OXO-5,6-DIHYDROPHENANTHRIDIN-2-YL)GLYCINAMIDE'>P34</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=7ski FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ski OCA], [https://pdbe.org/7ski PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ski RCSB], [https://www.ebi.ac.uk/pdbsum/7ski PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ski ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TOX1_BORPE TOX1_BORPE] S1 is an NAD-dependent ADP-ribosyltransferase, which plays a crucial role in the pathogenesis of B.pertussis causing disruption of normal host cellular regulation. It catalyzes the ADP-ribosylation of a cysteine in the alpha subunit of host heterotrimeric G proteins. In the absence of G proteins it also catalyzes the cleavage of NAD(+) into ADP-ribose and nicotinamide. It irreversibly uncouples the G-alpha GTP-binding proteins from their membrane receptors.
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== Publication Abstract from PubMed ==
Bordetella pertussis is the causative agent of whooping cough, a highly contagious respiratory disease. Pertussis toxin (PT), a major virulence factor secreted by B. pertussis, is an AB5-type protein complex topologically related to cholera toxin. The PT protein complex is internalized by host cells and follows a retrograde trafficking route to the endoplasmic reticulum (ER), where it subsequently dissociates. The released enzymatic S1 subunit is then translocated from the ER into the cytosol and subsequently ADP-ribosylates the inhibitory alpha-subunits (Galphai) of heterotrimeric G proteins, thus promoting dysregulation of G-protein coupled receptor (GPCR) signaling. However, the mechanistic details of the ADP-ribosylation activity of PT are not well understood. Here, we describe crystal structures of the S1 subunit in complex with nicotinamide adenine dinucleotide (NAD+), with NAD+ hydrolysis products ADP-ribose and nicotinamide, with NAD+ analog PJ34, and with a novel NAD+ analog formed upon S1 subunit crystallization with 3-amino benzamide (3AB) and NAD+, which we name benzamide amino adenine dinucleotide (BaAD). These crystal structures provide unprecedented insights into pre- and post-NAD+ hydrolysis steps of the ADP-ribosyltransferase activity of PT. We propose that these data may aid in rational drug design approaches and further development of PT-specific small molecule inhibitors.

Crystal structures of pertussis toxin with NAD(+) and analogs provide structural insights into the mechanism of its cytosolic ADP-ribosylation activity.,Sakari M, Tran MT, Rossjohn J, Pulliainen AT, Beddoe T, Littler DR J Biol Chem. 2022 Apr 1:101892. doi: 10.1016/j.jbc.2022.101892. PMID:35378130<ref>PMID:35378130</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 7ski" style="background-color:#fffaf0;"></div>

==See Also==
*[[Pertussis toxin|Pertussis toxin]]
== References ==
<references/>
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</StructureSection>
[[Category: Bordetella pertussis]]
[[Category: Large Structures]]
[[Category: Beddoe T]]
[[Category: Littler DR]]
[[Category: Pulliainen A]]
[[Category: Rossjohn J]]