Structural Integrity of the A147T Polymorph of Mammalian TSPO

Mariusz Jaremko, Lukasz Jaremko, Karin Giller, Stefan Becker, Markus Zweckstetter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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 languageEnglish (US)
Pages (from-to)1483-1489
Number of pages7
JournalChemBioChem
Volume16
Issue number10
DOIs
StatePublished - Jul 1 2015

Keywords

  • NMR spectroscopy
  • dynamics
  • membrane proteins
  • polymorphism
  • protein structures

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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