title: Protein structure. Structure and activity of tryptophan-rich TSPO proteins.
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.
authors: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors: Youzhong
authors: Y
authors: Guo
authors: The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA.
authors: Ravi C
authors: RC
authors: Kalathur
authors: The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. New York Structural Biology Center, Synchrotron Beamlines, Brookhaven National Laboratory, Upton, NY 11973, USA.
authors: Qun
authors: Q
authors: Liu
authors: The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA.
authors: Brian
authors: B
authors: Kloss
authors: The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA.
authors: Renato
authors: R
authors: Bruni
authors: The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA.
authors: Christopher
authors: C
authors: Ginter
authors: The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. Department of Informatics, Bioinformatics and Computational Biology, Technische Universität München, Garching 85748, Germany.
authors: Edda
authors: E
authors: Kloppmann
authors: The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. Department of Informatics, Bioinformatics and Computational Biology, Technische Universität München, Garching 85748, Germany.
authors: Burkhard
authors: B
authors: Rost
authors: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. New York Structural Biology Center, Synchrotron Beamlines, Brookhaven National Laboratory, Upton, NY 11973, USA. Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. wayne@xtl.cumc.columbia.edu.
authors: Wayne A
authors: WA
authors: Hendrickson
mesh_terms: D000595:Amino Acid Sequence; D001409:Bacillus cereus / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D007546:Isoquinolines / Q000378:metabolism; D008024:Ligands; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry; D011524:Protoporphyrins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014364:Tryptophan / Q000032:analysis
chemical_list: D001426:Bacterial Proteins; D007546:Isoquinolines; D008024:Ligands; D026901:Membrane Transport Proteins; D050505:Mutant Proteins; D021122:Protein Subunits; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D014364:Tryptophan; C028025:protoporphyrin IX; C037850:PK 11195
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