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Structural Integrity of the A147T Polymorph of Mammalian TSPO
Author(s) -
Jaremko Mariusz,
Jaremko Łukasz,
Giller Karin,
Becker Stefan,
Zweckstetter Markus
Publication year - 2015
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500217
Subject(s) - translocator protein , transmembrane protein , chemistry , ligand (biochemistry) , biophysics , structural integrity , inflammation , transmembrane domain , microbiology and biotechnology , biochemistry , computational biology , biology , receptor , neuroinflammation , immunology , structural engineering , engineering
Ligands of the transmembrane protein TSPO are used for imaging of brain inflammation, but a common polymorphism in TSPO complicates their application to humans. Here we determined the three‐dimensional structure and side‐chain dynamics of the A147T polymorph of mammalian TSPO in complex with the first‐generation ligand PK11195. We show that A147T TSPO is able to retain the same structural and dynamic profile as the wild‐type protein and thus binds PK11195 with comparable affinity. Our study is important for the design of more potent diagnostic and therapeutic ligands of TSPO.