4RYI

Crystal structure of BcTSPO/PK11195 complex

4RYI の概要

• エントリーDOI: 10.2210/pdb4ryi/pdb
• 関連するPDBエントリー: 4RYJ 4RYM 4RYN 4RYO
• 分子名称: Integral membrane protein, N-[(2R)-butan-2-yl]-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide (2 entities in total)
• 機能のキーワード: structural genomics, psi-biology, protein structure initiative, new york consortium on membrane protein structure, nycomps, receptor, membrane protein
• 由来する生物種: Bacillus cereus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 43699.64

構造登録者

Guo, Y.,Liu, Q.,Hendrickson, W.A.,New York Consortium on Membrane Protein Structure (NYCOMPS) (登録日: 2014-12-15, 公開日: 2015-01-28, 最終更新日: 2024-02-28)

主引用文献

Guo, Y.,Kalathur, R.C.,Liu, Q.,Kloss, B.,Bruni, R.,Ginter, C.,Kloppmann, E.,Rost, B.,Hendrickson, W.A.
Protein structure. Structure and activity of tryptophan-rich TSPO proteins.
Science, 347:551-555, 2015

PubMed 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.

PubMed: 25635100
DOI: 10.1126/science.aaa1534

実験手法

X-RAY DIFFRACTION (3.49 Å)