000207477 001__ 207477 000207477 005__ 20250730145808.0 000207477 0247_ $$2doi$$a10.1016/j.jsb.2014.10.002 000207477 0247_ $$2ISSN$$a1047-8477 000207477 0247_ $$2ISSN$$a1095-8657 000207477 0247_ $$2WOS$$aWOS:000346229500007 000207477 0247_ $$2pmid$$apmid:25450593 000207477 0247_ $$2openalex$$aopenalex:W2047628885 000207477 037__ $$aPUBDB-2015-01365 000207477 082__ $$a540 000207477 1001_ $$0P:(DE-H253)PIP1020528$$aDas, Uddipan$$b0$$eCorresponding Author 000207477 245__ $$aCrystal Structure of the VapBC-15 Complex from Mycobacterium Tuberculosis Reveals a Two-Metal Ion dependent PIN-Domain Ribonuclease and a Variable Mode of Toxin-Antitoxin Assemblypetea 000207477 260__ $$aSan Diego, Calif.$$bElsevier$$c2014 000207477 3367_ $$00$$2EndNote$$aJournal Article 000207477 3367_ $$2DRIVER$$aarticle 000207477 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1445000390_3746 000207477 3367_ $$2BibTeX$$aARTICLE 000207477 500__ $$3POF3_Assignment on 2016-02-15 000207477 500__ $$3POF3_Prefill: G:(DE-HGF)POF3-899 000207477 500__ $$a(c) Elsevier Inc. Post referee full text in progress. Embargo for full text 1 year from 22. Oct. 2014. 000207477 520__ $$aAlthough PIN (PilT N-terminal)-domain proteins are known to have ribonuclease activity, their specific mechanism of action remains unknown. VapCs form a family of ribonucleases that possess a PIN-domain assembly and are known as toxins. The activities of VapCs are impaired by VapB antitoxins. Here we present the crystal structure of the VapBC-15 toxin–antitoxin complex from Mycobacterium tuberculosis determined to 2.1 Å resolution. The VapB-15 and VapC-15 components assemble into one heterotetramer (VapB$_2$C$_2$) and two heterotrimers (VapBC$_2$) in each asymmetric unit of the crystal. The active site of VapC-15 toxin consists of a cluster of acidic amino acid residues and two divalent metal ions, forming a well organised ribonuclease active site. The distribution of the catalytic-site residues of the VapC-15 toxin is similar to that of T4 RNase H and of Methanococcus jannaschii FEN-1, providing strong evidence that these three proteins share a similar mechanism of activity. The presence of both VapB$_2$C$_2$ and VapBC$_2$ emphasizes the fact that the same antitoxin can bind the toxin in 1:1 and 1:2 ratios. The crystal structure determination of the VapBC-15 complex reveals for the first time a PIN-domain ribonuclease protein that shows two metal ions at the active site and a variable mode of toxin–antitoxin assembly. The structure further shows that VapB-15 antitoxin binds to the same groove meant for the binding of putative substrate (RNA), resulting in the inhibition of VapC-15’s toxicity. 000207477 536__ $$0G:(DE-H253)POF2-P13-20130405$$aPETRA Beamline P13 (POF2-54G14)$$cPOF2-54G14$$fPOF II$$x0 000207477 588__ $$aDataset connected to CrossRef, bib-pubdb1.desy.de 000207477 693__ $$0EXP:(DE-H253)P-P13-20150101$$1EXP:(DE-H253)PETRAIII-20150101$$6EXP:(DE-H253)P-P13-20150101$$aPETRA III$$fPETRA Beamline P13$$x0 000207477 7001_ $$0P:(DE-H253)PIP1013622$$aPogenberg, Vivian$$b1 000207477 7001_ $$0P:(DE-HGF)0$$aSubhramanyam, Udaya Kumar Tiruttani$$b2 000207477 7001_ $$0P:(DE-H253)PIP1001283$$aWilmanns, Matthias$$b3 000207477 7001_ $$0P:(DE-HGF)0$$aGourinath, Samudrala$$b4 000207477 7001_ $$0P:(DE-HGF)0$$aSrinivasan, Alagiri$$b5 000207477 773__ $$0PERI:(DE-600)1469822-5$$a10.1016/j.jsb.2014.10.002$$gVol. 188, no. 3, p. 249 - 258$$n3$$p249 - 258$$tJournal of structural biology$$v188$$x1047-8477$$y2014 000207477 8564_ $$uhttps://bib-pubdb1.desy.de/record/207477/files/10.1016_j.jsb.2014.10.002.pdf$$yRestricted 000207477 8564_ $$uhttps://bib-pubdb1.desy.de/record/207477/files/10.1016_j.jsb.2014.10.002.gif?subformat=icon$$xicon$$yRestricted 000207477 8564_ $$uhttps://bib-pubdb1.desy.de/record/207477/files/10.1016_j.jsb.2014.10.002.jpg?subformat=icon-1440$$xicon-1440$$yRestricted 000207477 8564_ $$uhttps://bib-pubdb1.desy.de/record/207477/files/10.1016_j.jsb.2014.10.002.jpg?subformat=icon-180$$xicon-180$$yRestricted 000207477 8564_ $$uhttps://bib-pubdb1.desy.de/record/207477/files/10.1016_j.jsb.2014.10.002.jpg?subformat=icon-640$$xicon-640$$yRestricted 000207477 8564_ $$uhttps://bib-pubdb1.desy.de/record/207477/files/10.1016_j.jsb.2014.10.002.jpg?subformat=icon-700$$xicon-700$$yRestricted 000207477 8564_ $$uhttps://bib-pubdb1.desy.de/record/207477/files/10.1016_j.jsb.2014.10.002.pdf?subformat=pdfa$$xpdfa$$yRestricted 000207477 909CO $$ooai:bib-pubdb1.desy.de:207477$$pVDB 000207477 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR 000207477 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000207477 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000207477 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000207477 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List 000207477 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000207477 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000207477 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000207477 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz 000207477 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences 000207477 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record 000207477 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews 000207477 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5 000207477 9141_ $$y2014 000207477 9132_ $$0G:(DE-HGF)POF3-622$$1G:(DE-HGF)POF3-620$$2G:(DE-HGF)POF3-600$$9G:(DE-HGF)POF3-6G3$$aDE-HGF$$bForschungsbereich Materie$$lVon Materie zu Materialien und Leben$$vFacility topic: Research on Matter with Brilliant Light Sources$$x0 000207477 9131_ $$0G:(DE-HGF)POF2-54G14$$1G:(DE-HGF)POF2-540$$2G:(DE-HGF)POF2-500$$3G:(DE-HGF)POF2$$4G:(DE-HGF)POF$$9G:(DE-H253)POF2-P13-20130405$$aDE-H253$$bStruktur der Materie$$lForschung mit Photonen, Neutronen, Ionen$$vPETRA III$$x0 000207477 9101_ $$0I:(DE-HGF)0$$6P:(DE-H253)PIP1020528$$aExternes Institut$$b0$$k>Extern 000207477 9101_ $$0I:(DE-588b)235011-7$$6P:(DE-H253)PIP1013622$$aEuropäisches Laboratorium für Molekularbiologie$$b1$$kEMBL 000207477 9101_ $$0I:(DE-HGF)0$$6P:(DE-H253)PIP1013622$$aExternes Institut$$b1$$k>Extern 000207477 9101_ $$0I:(DE-588b)235011-7$$6P:(DE-H253)PIP1001283$$aEuropäisches Laboratorium für Molekularbiologie$$b3$$kEMBL 000207477 9101_ $$0I:(DE-HGF)0$$6P:(DE-H253)PIP1001283$$aExternes Institut$$b3$$k>Extern 000207477 9201_ $$0I:(DE-H253)EMBL-20120731$$kEMBL$$lEMBL$$x0 000207477 980__ $$ajournal 000207477 980__ $$aVDB 000207477 980__ $$aI:(DE-H253)EMBL-20120731 000207477 980__ $$aUNRESTRICTED