% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Das:207477, author = {Das, Uddipan and Pogenberg, Vivian and Subhramanyam, Udaya Kumar Tiruttani and Wilmanns, Matthias and Gourinath, Samudrala and Srinivasan, Alagiri}, title = {{C}rystal {S}tructure of the {V}ap{BC}-15 {C}omplex from {M}ycobacterium {T}uberculosis {R}eveals a {T}wo-{M}etal {I}on dependent {PIN}-{D}omain {R}ibonuclease and a {V}ariable {M}ode of {T}oxin-{A}ntitoxin {A}ssemblypetea}, journal = {Journal of structural biology}, volume = {188}, number = {3}, issn = {1047-8477}, address = {San Diego, Calif.}, publisher = {Elsevier}, reportid = {PUBDB-2015-01365}, pages = {249 - 258}, year = {2014}, note = {(c) Elsevier Inc. Post referee full text in progress. Embargo for full text 1 year from 22. Oct. 2014.}, abstract = {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 2.1 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.}, cin = {EMBL}, ddc = {540}, cid = {I:(DE-H253)EMBL-20120731}, pnm = {PETRA Beamline P13 (POF2-54G14)}, pid = {G:(DE-H253)POF2-P13-20130405}, experiment = {EXP:(DE-H253)P-P13-20150101}, typ = {PUB:(DE-HGF)16}, UT = {WOS:000346229500007}, pubmed = {pmid:25450593}, doi = {10.1016/j.jsb.2014.10.002}, url = {https://bib-pubdb1.desy.de/record/207477}, }