Structural Integrity of the A147T Polymorph of Mammalian TSPO

Mariusz Jaremko; Łukasz Jaremko; Karin Giller; Stefan Becker; Markus Zweckstetter

doi:10.1002/cbic.201500217

Structural Integrity of the A147T Polymorph of Mammalian TSPO

Mariusz Jaremko
, Łukasz Jaremko
, Karin Giller
, Stefan Becker
, Markus Zweckstetter

Research output: Contribution to journal › Article › peer-review

30 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 language	English (US)
Pages (from-to)	1483-1489
Number of pages	7
Journal	ChemBioChem
Volume	16
Issue number	10
DOIs	https://doi.org/10.1002/cbic.201500217
State	Published - Jul 1 2015
Externally published	Yes

Keywords

dynamics
membrane proteins
NMR spectroscopy
polymorphism
protein structures

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Organic Chemistry

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10.1002/cbic.201500217

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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.",

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AU - Jaremko, Mariusz

AU - Jaremko, Łukasz

AU - Giller, Karin

AU - Becker, Stefan

AU - Zweckstetter, Markus

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 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.

AB - 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.

KW - dynamics

KW - membrane proteins

KW - NMR spectroscopy

KW - polymorphism

KW - protein structures

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JO - ChemBioChem

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Structural Integrity of the A147T Polymorph of Mammalian TSPO

Abstract

Keywords

ASJC Scopus subject areas

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