7UTF

Structure-Function characterization of an aldo-keto reductase involved in detoxification of the mycotoxin, deoxynivalenol

7UTF の概要

• エントリーDOI: 10.2210/pdb7utf/pdb
• 分子名称: Putative oxidoreductase, aryl-alcohol dehydrogenase like protein, SULFATE ION, CITRATE ANION, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, tim barrel, don epimerization, detoxification
• 由来する生物種: Rhizobium leguminosarum
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 162402.48

構造登録者

Abraham, N.,Schroeter, K.L.,Kimber, M.S.,Seah, S.Y.K. (登録日: 2022-04-26, 公開日: 2022-09-07, 最終更新日: 2023-10-18)

主引用文献

Abraham, N.,Schroeter, K.L.,Zhu, Y.,Chan, J.,Evans, N.,Kimber, M.S.,Carere, J.,Zhou, T.,Seah, S.Y.K.
Structure-function characterization of an aldo-keto reductase involved in detoxification of the mycotoxin, deoxynivalenol.
Sci Rep, 12:14737-14737, 2022

PubMed Abstract: Deoxynivalenol (DON) is a mycotoxin, produced by filamentous fungi such as Fusarium graminearum, that causes significant yield losses of cereal grain crops worldwide. One of the most promising methods to detoxify this mycotoxin involves its enzymatic epimerization to 3-epi-DON. DepB plays a critical role in this process by reducing 3-keto-DON, an intermediate in the epimerization process, to 3-epi-DON. DepB from Rhizobium leguminosarum is a member of the new aldo-keto reductase family, AKR18, and it has the unusual ability to utilize both NADH and NADPH as coenzymes, albeit with a 40-fold higher catalytic efficiency with NADPH compared to NADH. Structural analysis of DepB revealed the putative roles of Lys-217, Arg-290, and Gln-294 in NADPH specificity. Replacement of these residues by site-specific mutagenesis to negatively charged amino acids compromised NADPH binding with minimal effects on NADH binding. The substrate-binding site of DepB is larger than its closest structural homolog, AKR6A2, likely contributing to its ability to utilize a wide range of aldehydes and ketones, including the mycotoxin, patulin, as substrates. The structure of DepB also suggests that 3-keto-DON can adopt two binding modes to facilitate 4-pro-R hydride transfer to either the re- or si-face of the C3 ketone providing a possible explanation for the enzyme's ability to convert 3-keto-DON to 3-epi-DON and DON in diastereomeric ratios of 67.2% and 32.8% respectively.

PubMed: 36042239
DOI: 10.1038/s41598-022-19040-8

実験手法

X-RAY DIFFRACTION (2.5 Å)