TY  - JOUR
AU  - Das, Uddipan
AU  - Pogenberg, Vivian
AU  - Tiruttani Subhramanyam, Udaya Kumar
AU  - Matthias, Wilmanns
AU  - Gourinath, Samudrala
AU  - Srinivana, Alagiri
TI  - 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
JO  - Journal of structural biology
VL  - 188
IS  - 3
SN  - 1047-8477
CY  - San Diego, Calif.
PB  - Elsevier
M1  - FZJ-2014-05967
SP  - 249–258
PY  - 2014
N1  - Article in press
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000346229500007
DO  - DOI:10.1016/j.jsb.2014.10.002
UR  - https://juser.fz-juelich.de/record/172498
ER  -