Carnitine palmitoyltransferase 2: analysis of membrane association and complex structure with a substrate analog.

Arne C Rufer, Andrei Lomize, Jörg Benz, Odile Chomienne, Ralf Thoma, Michael Hennig

F Hoffmann-La Roche AG, Pharma Research Discovery, Basel, Switzerland.

FEBS letters 2007 Jul 10

filter terms:

The mitochondrial membrane-associated carnitine palmitoyltransferase system is a validated target for the treatment of type 2 diabetes mellitus. To further facilitate structure-based drug discovery, we determined the crystal structure of rat CPT-2 (rCPT-2) in complex with the substrate analogue palmitoyl-aminocarnitine at 1.8A resolution. Biochemical analyses revealed a strong effect of this compound on rCPT-2 activity and stability. Using a computational approach we examined the membrane association of rCPT-2. The protein interacts with the membrane as a functional monomer and the calculations confirm the presence of a membrane association domain that consists of layers of hydrophobic and positively charged residues.

Citation

Arne C Rufer, Andrei Lomize, Jörg Benz, Odile Chomienne, Ralf Thoma, Michael Hennig. Carnitine palmitoyltransferase 2: analysis of membrane association and complex structure with a substrate analog. FEBS letters. 2007 Jul 10;581(17):3247-52