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Article

Cardiolipin Stabilizes and Increases Catalytic Efficiency of Carnitine Palmitoyltransferase II and Its Variants S113L, P50H, and Y479F

1
Department of Neurology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany
2
Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120 Halle (Saale), Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Małgorzata Białek
Int. J. Mol. Sci. 2021, 22(9), 4831; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094831
Received: 25 March 2021 / Revised: 28 April 2021 / Accepted: 29 April 2021 / Published: 2 May 2021
(This article belongs to the Special Issue Enzymes and Mammalian Fatty Acid Metabolism)
Muscle carnitine palmitoyltransferase II (CPT II) deficiency is associated with various mutations in CPT2 gene. In the present study, the impact of the two CPT II variants P50H and Y479F were characterized in terms of stability and activity in vitro in comparison to wildtype (WT) and the well investigated variant S113L. While the initial enzyme activity of all variants showed wild-type-like behavior, the activity half-lives of the variants at different temperatures were severely reduced. This finding was validated by the investigation of thermostability of the enzymes using nano differential scanning fluorimetry (nanoDSF). Further, it was studied whether the protein stabilizing diphosphatidylglycerol cardiolipin (CL) has an effect on the variants. CL indeed had a positive effect on the stability. This effect was strongest for WT and least pronounced for variant P50H. Additionally, CL improved the catalytic efficiency for CPT II WT and the investigated variants by twofold when carnitine was the varied substrate due to a decrease in KM. However, there was no influence detected for the variation of substrate palmitoyl-CoA. The functional consequences of the stabilization by CL in vivo remain open. View Full-Text
Keywords: carnitine palmitoyltransferase II; cardiolipin; thermostability; S113L; P50H; Y479F; protein stability; muscle disease; CPT II deficiency carnitine palmitoyltransferase II; cardiolipin; thermostability; S113L; P50H; Y479F; protein stability; muscle disease; CPT II deficiency
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MDPI and ACS Style

Meinhardt, B.; Motlagh Scholle, L.; Seifert, F.; Anwand, M.; Pietzsch, M.; Zierz, S. Cardiolipin Stabilizes and Increases Catalytic Efficiency of Carnitine Palmitoyltransferase II and Its Variants S113L, P50H, and Y479F. Int. J. Mol. Sci. 2021, 22, 4831. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094831

AMA Style

Meinhardt B, Motlagh Scholle L, Seifert F, Anwand M, Pietzsch M, Zierz S. Cardiolipin Stabilizes and Increases Catalytic Efficiency of Carnitine Palmitoyltransferase II and Its Variants S113L, P50H, and Y479F. International Journal of Molecular Sciences. 2021; 22(9):4831. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094831

Chicago/Turabian Style

Meinhardt, Beate, Leila Motlagh Scholle, Franziska Seifert, Martina Anwand, Markus Pietzsch, and Stephan Zierz. 2021. "Cardiolipin Stabilizes and Increases Catalytic Efficiency of Carnitine Palmitoyltransferase II and Its Variants S113L, P50H, and Y479F" International Journal of Molecular Sciences 22, no. 9: 4831. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094831

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