Carnitine Palmitoyltransferase 2: Analysis of Membrane Association and Complex Structure with a Substrate Analog.
From: F Hoffmann-La Roche AG, Pharma Research Discovery, Basel, Switzerland.
FEBS letters
- Publish Date: Jul 2007
- ISSN: 0014-5793
- Volume: 581
- Issue: 17
- Pages: 3247-52
- Medium: Print
- Language: English
- Citation (JAMA): Rufer Arne C, Lomize Andrei, Benz Jörg, et al. Carnitine Palmitoyltransferase 2: Analysis of Membrane Association and Complex Structure with a Substrate Analog.. FEBS Lett. Jul 2007;581:3247-52
Abstract
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.
Mesh Headings (Keywords): Animals, Binding Sites, Carnitine, Carnitine O-Palmitoyltransferase, Crystallography, X-Ray, Mitochondrial Membranes, Models, Molecular, Models, Theoretical, Protein Binding, Protein Denaturation, Rats, Substrate Specificity
Check for Full Text / PubMed Unique Identifier (PMID): 17585909
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