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==CRYSTAL STRUCTURE OF GENETICALLY DETOXIFIED PERTUSSIS TOXIN GDPT.== | ==CRYSTAL STRUCTURE OF GENETICALLY DETOXIFIED PERTUSSIS TOXIN GDPT.== | ||
<StructureSection load='6ro0' size='340' side='right'caption='[[6ro0]]' scene=''> | <StructureSection load='6ro0' size='340' side='right'caption='[[6ro0]], [[Resolution|resolution]] 2.13Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RO0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6RO0 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6ro0]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacterium_tussis-convulsivae"_lehmann_and_neumann_1927 "bacterium tussis-convulsivae" lehmann and neumann 1927]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RO0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6RO0 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ro0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ro0 OCA], [http://pdbe.org/6ro0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ro0 RCSB], [http://www.ebi.ac.uk/pdbsum/6ro0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ro0 ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ptxA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=520 "Bacterium tussis-convulsivae" Lehmann and Neumann 1927]), ptxB, CYO81_20230, ERS004697_00332, ERS004704_00067, ERS004709_00223, ERS005128_00199, ERS005179_00182, ERS014547_00750, NCTC10911_00247 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=520 "Bacterium tussis-convulsivae" Lehmann and Neumann 1927]), ptxS3, ptxC, ptxC_1, ptxC_2, CYO81_20245, ERS004697_00106, ERS004704_00094, ERS004709_00174, ERS005128_00196, ERS005179_00179, ERS014547_00747, ERS014550_01623, NCTC10911_00250 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=520 "Bacterium tussis-convulsivae" Lehmann and Neumann 1927]), ptxD, CYO81_20235, ERS005128_00198, ERS005179_00181, ERS014547_00749, NCTC10911_00248 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=520 "Bacterium tussis-convulsivae" Lehmann and Neumann 1927]), ptxE, ERS004697_00105, ERS004704_00093, ERS004709_00175, ERS005128_00197, ERS005179_00180, ERS014547_00748, ERS014550_01624, ERS018341_00090 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=520 "Bacterium tussis-convulsivae" Lehmann and Neumann 1927])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ro0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ro0 OCA], [http://pdbe.org/6ro0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ro0 RCSB], [http://www.ebi.ac.uk/pdbsum/6ro0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ro0 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/C0MPK8_BORPT C0MPK8_BORPT]] PTX oligomer B binds to receptors on the eukaryotic cell surface and facilitates the translocation of the toxic subunit across the cell membrane.[ARBA:ARBA00002398] [[http://www.uniprot.org/uniprot/Q546I1_BORPT Q546I1_BORPT]] PTX oligomer B binds to receptors on the eukaryotic cell surface and facilitates the translocation of the toxic subunit across the cell membrane.[ARBA:ARBA00002398] [[http://www.uniprot.org/uniprot/A0A0E8DFW5_BORPT A0A0E8DFW5_BORPT]] PTX oligomer B binds to receptors on the eukaryotic cell surface and facilitates the translocation of the toxic subunit across the cell membrane.[ARBA:ARBA00002398] [[http://www.uniprot.org/uniprot/C0MPK9_BORPT C0MPK9_BORPT]] PTX oligomer B binds to receptors on the eukaryotic cell surface and facilitates the translocation of the toxic subunit across the cell membrane.[ARBA:ARBA00002398] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The mutant gdPT R9K/E129G is a genetically detoxified variant of the pertussis toxin (PTx) and represents an attractive candidate for the development of improved pertussis vaccines. The impact of the mutations on the overall protein structure and its immunogenicity has remained elusive. Here we present the crystal structure of gdPT and show that it is nearly identical to that of PTx. Hydrogen-deuterium exchange mass spectrometry revealed dynamic changes in the catalytic domain that directly impacted NAD(+) binding which was confirmed by biolayer interferometry. Distal changes in dynamics were also detected in S2-S5 subunit interactions resulting in tighter packing of B-oligomer corresponding to increased thermal stability. Finally, antigen stimulation of human whole blood, analyzed by a previously unreported mass cytometry assay, indicated broader immunogenicity of gdPT compared to pertussis toxoid. These findings establish a direct link between the conserved structure of gdPT and its ability to generate a robust immune response. | |||
Genetically detoxified pertussis toxin displays near identical structure to its wild-type and exhibits robust immunogenicity.,Ausar SF, Zhu S, Duprez J, Cohen M, Bertrand T, Steier V, Wilson DJ, Li S, Sheung A, Brookes RH, Pedyczak A, Rak A, Andrew James D Commun Biol. 2020 Aug 5;3(1):427. doi: 10.1038/s42003-020-01153-3. PMID:32759959<ref>PMID:32759959</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6ro0" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacterium tussis-convulsivae lehmann and neumann 1927]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bertrand, T]] | [[Category: Bertrand, T]] | ||
[[Category: Toxin]] | |||