% 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:172498, author = {Das, Uddipan and Pogenberg, Vivian and Tiruttani Subhramanyam, Udaya Kumar and Matthias, Wilmanns and Gourinath, Samudrala and Srinivana, Alagiri}, title = {{C}rystal structure of the {V}ap{BC}-15 complex from {M}ycobacterium tuberculosis reveals a two-metal ion dependent {PIN}-domain ribonuclease and a variable mode of toxin-antitoxin assembly}, journal = {Journal of structural biology}, volume = {188}, number = {3}, issn = {1047-8477}, address = {San Diego, Calif.}, publisher = {Elsevier}, reportid = {FZJ-2014-05967}, pages = {249–258}, year = {2014}, note = {Article in press}, 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 (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.}, cin = {ICS-6}, ddc = {540}, cid = {I:(DE-Juel1)ICS-6-20110106}, pnm = {452 - Structural Biology (POF2-452)}, pid = {G:(DE-HGF)POF2-452}, typ = {PUB:(DE-HGF)16}, UT = {WOS:000346229500007}, doi = {10.1016/j.jsb.2014.10.002}, url = {https://juser.fz-juelich.de/record/172498}, }