Science 2015-01-30

Protein structure. Structure and activity of tryptophan-rich TSPO proteins.

Youzhong Guo, Ravi C Kalathur, Qun Liu, Brian Kloss, Renato Bruni, Christopher Ginter, Edda Kloppmann, Burkhard Rost, Wayne A Hendrickson

Index: Science 347(6221) , 551-5, (2015)

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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. Copyright © 2015, American Association for the Advancement of Science.