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Science
2015 Jan 30;3476221:551-5. doi: 10.1126/science.aaa1534.
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Protein structure. Structure and activity of tryptophan-rich TSPO proteins.
Guo Y
,
Kalathur RC
,
Liu Q
,
Kloss B
,
Bruni R
,
Ginter C
,
Kloppmann E
,
Rost B
,
Hendrickson WA
.
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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.
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