%0 Journal Article %1 Guo2015TSPOStructure %A Guo, Youzhong %A Kalathur, Ravi C. %A Liu, Qun %A Kloss, Brian %A Bruni, Renato %A Ginter, Christopher %A Kloppmann, Edda %A Rost, Burkhard %A Hendrickson, Wayne A. %D 2015 %J Science %K crystallography tspo %N 6221 %P 551-555 %T Structure and activity of tryptophan-rich TSPO proteins %U http://science.sciencemag.org/content/347/6221/551 %V 347 %X Translocator proteins (TSPOs) bind steroids and porphyrins, and they are implicated in many human diseases, for which they serve as biomarkers and therapeutic targets. TSPOs have tryptophan-rich sequences that are highly conserved from bacteria to mammals. Here we report crystal structures for Bacillus cereus TSPO (BcTSPO) down to 1.7 Å resolution, including a complex with the benzodiazepine-like inhibitor PK11195. We also describe BcTSPO-mediated protoporphyrin IX (PpIX) reactions, including catalytic degradation to a previously undescribed heme derivative. We used structure-inspired mutations to investigate reaction mechanisms, and we showed that TSPOs from Xenopus and man have similar PpIX-directed activities. Although TSPOs have been regarded as transporters, the catalytic activity in PpIX degradation suggests physiological importance for TSPOs in protection against oxidative stress.

@article{Guo2015TSPOStructure, abstract = {Translocator proteins (TSPOs) bind steroids and porphyrins, and they are implicated in many human diseases, for which they serve as biomarkers and therapeutic targets. TSPOs have tryptophan-rich sequences that are highly conserved from bacteria to mammals. Here we report crystal structures for Bacillus cereus TSPO (BcTSPO) down to 1.7 Å resolution, including a complex with the benzodiazepine-like inhibitor PK11195. We also describe BcTSPO-mediated protoporphyrin IX (PpIX) reactions, including catalytic degradation to a previously undescribed heme derivative. We used structure-inspired mutations to investigate reaction mechanisms, and we showed that TSPOs from Xenopus and man have similar PpIX-directed activities. Although TSPOs have been regarded as transporters, the catalytic activity in PpIX degradation suggests physiological importance for TSPOs in protection against oxidative stress.}, added-at = {2016-01-12T22:09:58.000+0100}, author = {Guo, Youzhong and Kalathur, Ravi C. and Liu, Qun and Kloss, Brian and Bruni, Renato and Ginter, Christopher and Kloppmann, Edda and Rost, Burkhard and Hendrickson, Wayne A.}, biburl = {https://www.bibsonomy.org/bibtex/2a2cc941156d8c643b437da3fafb3ac25/salotz}, description = {Structure and activity of tryptophan-rich TSPO proteins | Science}, interhash = {09e3708cfd295ab99b5833c2f404e138}, intrahash = {a2cc941156d8c643b437da3fafb3ac25}, journal = {Science}, keywords = {crystallography tspo}, month = {January}, number = 6221, pages = {551-555}, timestamp = {2016-01-12T22:09:58.000+0100}, title = {Structure and activity of tryptophan-rich TSPO proteins}, url = {http://science.sciencemag.org/content/347/6221/551}, volume = 347, year = 2015 }