【摘 要】
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Mitochondrial fatty acid synthesis (mtFAS) is essential for respiratory growth in yeast and mammalian embryonic survival.The human 3-ketoacyl-acyl carrier prote
【机 构】
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FacultyofBiochemistryandMolecularMedicineandBiocenterOuluUniversityofOulu,POBox,Oulu,FinlandStateKey
【出 处】
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4th International Supramolecular System Symposium(ISSS2015)(
论文部分内容阅读
Mitochondrial fatty acid synthesis (mtFAS) is essential for respiratory growth in yeast and mammalian embryonic survival.The human 3-ketoacyl-acyl carrier protein (ACP) reductase (KAR) of mtFAS is a heterotetrameric α2β2-assembly composed of 17β-hydroxysteroid dehydrogenase type-8 (HSD17B8, α-subunit) and carbonyl reductase type-4 (CBR4, β-subunit).Here we provide a structural explanation for the stability of the heterotetramer from the crystal structure with NAD+ and NADP+ bound to the HSD17B8 and CBR4 subunits,respectively, and show that the catalytic activity of the NADPH-and ACP-dependent CBR4 subunit is crucial for a functional HsKAR.Therefore, mtFAS is NADPH and ACP dependent,employing the 3R-hydroxyacyl-ACP intermediate.HSD17B8 assists in the formation of the competent HsKAR assembly.The intrinsic NADP-and CoA-dependent activity of the HSD17B8 subunit on the 3R-hydroxyacyl-CoA intermediates may indicate a role for this subunit in routing 3R-hydroxyacyl-CoA esters, potentially arising from the metabolism of unsaturated fatty acids, into the mitochondrial β-oxidation pathway.
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