Abstract
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.
Original language | English (US) |
---|---|
Pages (from-to) | 1483-1489 |
Number of pages | 7 |
Journal | ChemBioChem |
Volume | 16 |
Issue number | 10 |
DOIs | |
State | Published - Jul 1 2015 |
Externally published | Yes |
Keywords
- NMR spectroscopy
- dynamics
- membrane proteins
- polymorphism
- protein structures
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Organic Chemistry