5LBX

Structure of the T175V Etr1p mutant in the trigonal form P312 in complex with NADP and crotonyl-CoA

5LBX の概要

• エントリーDOI: 10.2210/pdb5lbx/pdb
• 分子名称: Enoyl-[acyl-carrier-protein] reductase [NADPH, B-specific] 1, mitochondrial, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: negative catalysis, enzyme, nadp, mitochondria, mutant, crotonyl-coa, reductase, oxidoreductase
• 由来する生物種: Candida tropicalis (Yeast)
• 細胞内の位置: Mitochondrion : Q8WZM3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 88616.62

構造登録者

Wagner, T.,Rosenthal, R.G.,Voegeli, B.,Shima, S.,Erb, T.J. (登録日: 2016-06-17, 公開日: 2017-05-10, 最終更新日: 2024-01-10)

主引用文献

Rosenthal, R.G.,Vogeli, B.,Wagner, T.,Shima, S.,Erb, T.J.
A conserved threonine prevents self-intoxication of enoyl-thioester reductases.
Nat. Chem. Biol., 13:745-749, 2017

PubMed Abstract: Enzymes are highly specific biocatalysts, yet they can promote unwanted side reactions. Here we investigated the factors that direct catalysis in the enoyl-thioester reductase Etr1p. We show that a single conserved threonine is essential to suppress the formation of a side product that would otherwise act as a high-affinity inhibitor of the enzyme. Substitution of this threonine with isosteric valine increases side-product formation by more than six orders of magnitude, while decreasing turnover frequency by only one order of magnitude. Our results show that the promotion of wanted reactions and the suppression of unwanted side reactions operate independently at the active site of Etr1p, and that the active suppression of side reactions is highly conserved in the family of medium-chain dehydrogenases/reductases (MDRs). Our discovery emphasizes the fact that the active destabilization of competing transition states is an important factor during catalysis that has implications for the understanding and the de novo design of enzymes.

PubMed: 28504678
DOI: 10.1038/nchembio.2375

実験手法

X-RAY DIFFRACTION (2.5 Å)