7AYC

Crystal Structure of human mitochondrial 2-Enoyl Thioester Reductase (MECR) with single mutation G165Q

7AYC の概要

• エントリーDOI: 10.2210/pdb7ayc/pdb
• 関連するPDBエントリー: 7AYB 7AYD
• 分子名称: Enoyl-[acyl-carrier-protein] reductase, mitochondrial, CHLORIDE ION (3 entities in total)
• 機能のキーワード: medium-chain alcohol dehydrogenase, mitochondrial trans-2-enoyl-coa reductase, fatty acid synthesis, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38470.43

構造登録者

Rahman, M.T.,Koski, M.K.,Autio, K.J.,Kastaniotis, A.J.,Wierenga, R.K.,Hiltunen, J.K. (登録日: 2020-11-12, 公開日: 2022-06-01, 最終更新日: 2024-02-07)

主引用文献

Tanvir Rahman, M.,Kristian Koski, M.,Panecka-Hofman, J.,Schmitz, W.,Kastaniotis, A.J.,Wade, R.C.,Wierenga, R.K.,Kalervo Hiltunen, J.,Autio, K.J.
An engineered variant of MECR reductase reveals indispensability of long-chain acyl-ACPs for mitochondrial respiration.
Nat Commun, 14:619-619, 2023

PubMed Abstract: Mitochondrial fatty acid synthesis (mtFAS) is essential for respiratory function. MtFAS generates the octanoic acid precursor for lipoic acid synthesis, but the role of longer fatty acid products has remained unclear. The structurally well-characterized component of mtFAS, human 2E-enoyl-ACP reductase (MECR) rescues respiratory growth and lipoylation defects of a Saccharomyces cerevisiae Δetr1 strain lacking native mtFAS enoyl reductase. To address the role of longer products of mtFAS, we employed in silico molecular simulations to design a MECR variant with a shortened substrate binding cavity. Our in vitro and in vivo analyses indicate that the MECR G165Q variant allows synthesis of octanoyl groups but not long chain fatty acids, confirming the validity of our computational approach to engineer substrate length specificity. Furthermore, our data imply that restoring lipoylation in mtFAS deficient yeast strains is not sufficient to support respiration and that long chain acyl-ACPs generated by mtFAS are required for mitochondrial function.

PubMed: 36739436
DOI: 10.1038/s41467-023-36358-7

実験手法

X-RAY DIFFRACTION (2.02 Å)