Structural Integrity of the A147T Polymorph of Mammalian TSPO

Chembiochem. 2015 Jul 6;16(10):1483-9. doi: 10.1002/cbic.201500217. Epub 2015 Jun 10.


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.

Keywords: NMR spectroscopy; dynamics; membrane proteins; polymorphism; protein structures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Humans
  • Isoquinolines / metabolism
  • Ligands
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Polymorphism, Single Nucleotide*
  • Protein Binding
  • Protein Conformation
  • Protein Folding
  • Receptors, GABA / chemistry*
  • Receptors, GABA / genetics*
  • Receptors, GABA / metabolism
  • Sequence Alignment


  • Bzrp protein, mouse
  • Isoquinolines
  • Ligands
  • Receptors, GABA
  • PK 11195