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| | ==Crystal structure of ADP-ribosyltransferase Vis in complex with NAD== | | ==Crystal structure of ADP-ribosyltransferase Vis in complex with NAD== |
| - | <StructureSection load='4xzj' size='340' side='right' caption='[[4xzj]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='4xzj' size='340' side='right'caption='[[4xzj]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4xzj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"photobacter_splendidum"_(sic)_beijerinck_1900 "photobacter splendidum" (sic) beijerinck 1900]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XZJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XZJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4xzj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_splendidus Vibrio splendidus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XZJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XZJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xzk|4xzk]]</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=4xzj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xzj OCA], [https://pdbe.org/4xzj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xzj RCSB], [https://www.ebi.ac.uk/pdbsum/4xzj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xzj ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">V12B01_18061 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=29497 "Photobacter splendidum" (sic) Beijerinck 1900])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)--protein-arginine_ADP-ribosyltransferase NAD(+)--protein-arginine ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.31 2.4.2.31] </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=4xzj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xzj OCA], [http://pdbe.org/4xzj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xzj RCSB], [http://www.ebi.ac.uk/pdbsum/4xzj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xzj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VIS_VIBSP VIS_VIBSP]] A probable mono(ADP-ribosyl)transferase, it may ADP-ribosylate Arg in target protein(s). Upon expression in yeast cells causes cell death.<ref>PMID:21170356</ref> | + | [https://www.uniprot.org/uniprot/VIS_VIBS1 VIS_VIBS1] A probable mono(ADP-ribosyl)transferase, it may ADP-ribosylate Arg in target protein(s). Upon expression in yeast cells causes cell death.<ref>PMID:21170356</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Merrill, A R]] | + | [[Category: Large Structures]] |
| - | [[Category: Pai, E F]] | + | [[Category: Vibrio splendidus]] |
| - | [[Category: Pfoh, R]] | + | [[Category: Merrill AR]] |
| - | [[Category: Ravulapalli, R]] | + | [[Category: Pai EF]] |
| - | [[Category: Transferase]] | + | [[Category: Pfoh R]] |
| | + | [[Category: Ravulapalli R]] |
| Structural highlights
Function
VIS_VIBS1 A probable mono(ADP-ribosyl)transferase, it may ADP-ribosylate Arg in target protein(s). Upon expression in yeast cells causes cell death.[1]
Publication Abstract from PubMed
Vis toxin was identified by a bioinformatics strategy as a putative virulence factor produced by Vibrio splendidus with mono-ADP-ribosyltransferase activity. Vis was purified to homogeneity as a 28 kDa single-domain enzyme and was shown to possess NAD(+)-glycohydrolase [KM(NAD(+)) = 276 +/- 12 muM] activity and with an R-S-E-X-E motif; it targets arginine-related compounds [KM(agmatine) = 272 +/- 18 mM]. Mass spectrometry analysis revealed that Vis labels l-arginine with ADP-ribose from the NAD(+) substrate at the amino nitrogen of the guanidinium side chain. Vis is toxic to yeast when expressed in the cytoplasm under control of the CUP1 promotor, and catalytic variants lost the ability to kill the yeast host, indicating that the toxin exerts its lethality through its enzyme activity. Several small molecule inhibitors were identified from a virtual screen, and the most potent compounds were found to inhibit the transferase activity of the enzyme with Ki values ranging from 25 to 134 muM. Inhibitor compound M6 bears the necessary attributes of a solid candidate as a lead compound for therapeutic development. Vis toxin was crystallized, and the structures of the apoenzyme (1.4 A) and the enzyme bound with NAD(+) (1.8 A) and with the M6 inhibitor (1.5 A) were determined. The structures revealed that Vis represents a new subgroup within the mono-ADP-ribosyltransferase toxin family.
Characterization of Vis Toxin, a Novel ADP-Ribosyltransferase from Vibrio splendidus.,Ravulapalli R, Lugo MR, Pfoh R, Visschedyk D, Poole A, Fieldhouse RJ, Pai EF, Merrill AR Biochemistry. 2015 Sep 29;54(38):5920-36. doi: 10.1021/acs.biochem.5b00921. Epub , 2015 Sep 17. PMID:26352925[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fieldhouse RJ, Turgeon Z, White D, Merrill AR. Cholera- and anthrax-like toxins are among several new ADP-ribosyltransferases. PLoS Comput Biol. 2010 Dec 9;6(12):e1001029. doi: 10.1371/journal.pcbi.1001029. PMID:21170356 doi:http://dx.doi.org/10.1371/journal.pcbi.1001029
- ↑ Ravulapalli R, Lugo MR, Pfoh R, Visschedyk D, Poole A, Fieldhouse RJ, Pai EF, Merrill AR. Characterization of Vis Toxin, a Novel ADP-Ribosyltransferase from Vibrio splendidus. Biochemistry. 2015 Sep 29;54(38):5920-36. doi: 10.1021/acs.biochem.5b00921. Epub , 2015 Sep 17. PMID:26352925 doi:http://dx.doi.org/10.1021/acs.biochem.5b00921
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