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| | <StructureSection load='4chg' size='340' side='right'caption='[[4chg]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='4chg' size='340' side='right'caption='[[4chg]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4chg]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CHG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CHG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4chg]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CHG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CHG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=4chg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4chg OCA], [https://pdbe.org/4chg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4chg RCSB], [https://www.ebi.ac.uk/pdbsum/4chg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4chg ProSAT]</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=4chg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4chg OCA], [http://pdbe.org/4chg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4chg RCSB], [http://www.ebi.ac.uk/pdbsum/4chg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4chg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VPC15_MYCTU VPC15_MYCTU]] Toxic component of a toxin-antitoxin (TA) module. An RNase (By similarity). Upon expression in M.smegmatis inhibits colony formation. Its toxic effect is neutralized by coexpression with cognate antitoxin VapB15.[HAMAP-Rule:MF_00265]<ref>PMID:20011113</ref> [[http://www.uniprot.org/uniprot/VPB15_MYCTU VPB15_MYCTU]] Antitoxin component of a toxin-antitoxin (TA) module. Upon expression in M.smegmatis neutralizes the effect of cognate toxin VapC15. | + | [[https://www.uniprot.org/uniprot/VPC15_MYCTU VPC15_MYCTU]] Toxic component of a toxin-antitoxin (TA) module. An RNase (By similarity). Upon expression in M.smegmatis inhibits colony formation. Its toxic effect is neutralized by coexpression with cognate antitoxin VapB15.[HAMAP-Rule:MF_00265]<ref>PMID:20011113</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Although PIN (PilT N-terminal)-domain proteins are known to have ribonuclease activity, their specific mechanism of action remains unknown. VapCs form a family of ribonucleases that possess a PIN-domain assembly and are known as toxins. The activities of VapCs are impaired by VapB antitoxins. Here we present the crystal structure of the VapBC-15 toxin-antitoxin complex from Mycobacterium tuberculosis determined to 2.1A resolution. The VapB-15 and VapC-15 components assemble into one heterotetramer (VapB2C2) and two heterotrimers (VapBC2) in each asymmetric unit of the crystal. The active site of VapC-15 toxin consists of a cluster of acidic amino acid residues and two divalent metal ions, forming a well organised ribonuclease active site. The distribution of the catalytic-site residues of the VapC-15 toxin is similar to that of T4 RNase H and of Methanococcus jannaschii FEN-1, providing strong evidence that these three proteins share a similar mechanism of activity. The presence of both VapB2C2 and VapBC2 emphasizes the fact that the same antitoxin can bind the toxin in 1:1 and 1:2 ratios. The crystal structure determination of the VapBC-15 complex reveals for the first time a PIN-domain ribonuclease protein that shows two metal ions at the active site and a variable mode of toxin-antitoxin assembly. The structure further shows that VapB-15 antitoxin binds to the same groove meant for the binding of putative substrate (RNA), resulting in the inhibition of VapC-15's toxicity.
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| - | | + | |
| - | Crystal structure of the VapBC-15 complex from Mycobacterium tuberculosis reveals a two-metal ion dependent PIN-domain ribonuclease and a variable mode of toxin-antitoxin assembly.,Das U, Pogenberg V, Subhramanyam UK, Wilmanns M, Gourinath S, Srinivasan A J Struct Biol. 2014 Oct 22;188(3):249-258. doi: 10.1016/j.jsb.2014.10.002. PMID:25450593<ref>PMID:25450593</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4chg" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Das, U]] | + | [[Category: Das U]] |
| - | [[Category: Gourinath, S]] | + | [[Category: Gourinath S]] |
| - | [[Category: Pogenberg, V]] | + | [[Category: Pogenberg V]] |
| - | [[Category: Srinivasan, A]] | + | [[Category: Srinivasan A]] |
| - | [[Category: Subhramanyam, U K.Tiruttani]] | + | [[Category: Tiruttani Subhramanyam UK]] |
| - | [[Category: Wilmanns, M]] | + | [[Category: Wilmanns M]] |
| - | [[Category: Pin domain]]
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| - | [[Category: Toxin-antitoxin complex]]
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