3ess

From Proteopedia

(Difference between revisions)

Revision as of 17:08, 2 January 2017

Catalytic fragment of Cholix toxin from Vibrio Cholerae in complex with the 1,8-Naphthalimide inhibitor

Structural highlights

3ess is a 1 chain structure with sequence from "bacillo_virgola_del_koch"_trevisan_1884 "bacillo virgola del koch" trevisan 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2q6m, 2q5t
Gene:	chxA, toxA ("Bacillo virgola del Koch" Trevisan 1884)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CHXA_VIBCL] An NAD-dependent ADP-ribosyltransferase (ADPRT), it catalyzes the transfer of the ADP-ribosyl moiety of oxidized NAD onto eukaryotic elongation factor 2 (eEF-2) thus arresting protein synthesis. It probably uses the eukaryotic prolow-density lipoprotein receptor-related protein 1 (LRP1) to enter mouse cells, although there seems to be at least one other receptor as well. Is active against mouse fibroblasts, Chinese hamster ovary eEF-2, brine shrimp (Artemia spp. nauplii) and upon expression in S.cerevisiae.^[1] ^[2]

Publication Abstract from PubMed

The emergence of bacterial antibiotic resistance poses a significant challenge in the pursuit of novel therapeutics, making new strategies for drug discovery imperative. We have developed a yeast growth-defect phenotypic screen to help solve this current dilemma. This approach facilitates the identification and characterization of a new diphtheria toxin (DT) group, ADP-ribosyltransferase toxins from pathogenic bacteria. In addition, this assay utilizes Saccharomyces cerevisiae, a reliable model for bacterial toxin expression, to streamline the identification and characterization of new inhibitors against this group of bacterial toxins that may be useful for antimicrobial therapies. We show that a mutant of the elongation factor 2 target protein in yeast, G701R, confers resistance to all DT group toxins and recovers the growth-defect phenotype in yeast. We also demonstrate the ability of a potent small-molecule toxin inhibitor, 1,8-naphthalimide (NAP), to alleviate the growth defect caused by toxin expression in yeast. Moreover, we determined the crystal structure of the NAP inhibitor-toxin complex at near-atomic resolution to provide insight into the inhibitory mechanism. Finally, the NAP inhibitor shows therapeutic protective effects against toxin invasion of mammalian cells, including human lung cells.

Yeast as a tool for characterizing mono-ADP-ribosyltransferase toxins.,Turgeon Z, White D, Jorgensen R, Visschedyk D, Fieldhouse RJ, Mangroo D, Merrill AR FEMS Microbiol Lett. 2009 Nov;300(1):97-106. Epub 2009 Aug 31. PMID:19793133^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Jorgensen R, Purdy AE, Fieldhouse RJ, Kimber MS, Bartlett DH, Rod Merrill A. Cholix toxin, a novel ADP-ribosylating factor from vibrio cholerae. J Biol Chem. 2008 Feb 25;. PMID:18276581 doi:M710008200
↑ Turgeon Z, White D, Jorgensen R, Visschedyk D, Fieldhouse RJ, Mangroo D, Merrill AR. Yeast as a tool for characterizing mono-ADP-ribosyltransferase toxins. FEMS Microbiol Lett. 2009 Nov;300(1):97-106. Epub 2009 Aug 31. PMID:19793133 doi:10.1111/j.1574-6968.2009.01777.x
↑ Turgeon Z, White D, Jorgensen R, Visschedyk D, Fieldhouse RJ, Mangroo D, Merrill AR. Yeast as a tool for characterizing mono-ADP-ribosyltransferase toxins. FEMS Microbiol Lett. 2009 Nov;300(1):97-106. Epub 2009 Aug 31. PMID:19793133 doi:10.1111/j.1574-6968.2009.01777.x

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ess"

@@ Line 1: / Line 1: @@
 ==Catalytic fragment of Cholix toxin from Vibrio Cholerae in complex with the 1,8-Naphthalimide inhibitor==
 <StructureSection load='3ess' size='340' side='right' caption='[[3ess]], [[Resolution|resolution]] 1.19&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2q6m|2q6m]], [[2q5t|2q5t]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">chxA, toxA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=666 "Bacillo virgola del Koch" Trevisan 1884])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ess FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ess OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ess RCSB], [http://www.ebi.ac.uk/pdbsum/3ess PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ess FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ess OCA], [http://pdbe.org/3ess PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ess RCSB], [http://www.ebi.ac.uk/pdbsum/3ess PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ess ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3ess" style="background-color:#fffaf0;"></div>
 ==See Also==

3ess

From Proteopedia

Revision as of 17:08, 2 January 2017

Catalytic fragment of Cholix toxin from Vibrio Cholerae in complex with the 1,8-Naphthalimide inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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