4CQL

Crystal structure of heterotetrameric human ketoacyl reductase complexed with NAD

4CQL の概要

• エントリーDOI: 10.2210/pdb4cql/pdb
• 関連するPDBエントリー: 4CQM
• 分子名称: ESTRADIOL 17-BETA-DEHYDROGENASE 8, CARBONYL REDUCTASE FAMILY MEMBER 4, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, kar, 3-ketoacyl-acp reductase, hsd8, 17-beta hydroxysteroid dehydrogenase, hsd17b8, 3r- hydroxyacyl-coa dehydrogenase, carbobyl reductase type4, nadh, nadp, nadph, hetero tetramer
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Mitochondrion matrix: Q92506 Q8N4T8
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 431693.35

構造登録者

Venkatesan, R.,Sah-Teli, S.K.,Awoniyi, L.O.,Jiang, G.,Prus, P.,Kastaniotis, A.J.,Hiltunen, J.K.,Wierenga, R.K.,Chen, Z. (登録日: 2014-02-19, 公開日: 2014-09-10, 最終更新日: 2023-12-20)

主引用文献

Venkatesan, R.,Sah-Teli, S.K.,Awoniyi, L.O.,Jiang, G.,Prus, P.,Kastaniotis, A.J.,Hiltunen, J.K.,Wierenga, R.K.,Chen, Z.
Insights Into Mitochondrial Fatty Acid Synthesis from the Structure of Heterotetrameric 3-Ketoacyl-Acp Reductase/3R-Hydroxyacyl-Coa Dehydrogenase.
Nat.Commun., 5:4805-, 2014

PubMed Abstract: 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 NAD(+)- 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.

PubMed: 25203508
DOI: 10.1038/NCOMMS5805

実験手法

X-RAY DIFFRACTION (2.85 Å)