7W61

Crystal structure of farnesol dehydrogenase from Helicoverpa armigera

7W61 の概要

• エントリーDOI: 10.2210/pdb7w61/pdb
• 分子名称: Farnesol dehydrogenase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ACETATE ION, ... (7 entities in total)
• 機能のキーワード: short chain dehydrogenase, oxidoreductase
• 由来する生物種: Helicoverpa armigera
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27587.00

構造登録者

Kumar, R.,Das, J.,Mahto, J.K.,Sharma, M.,Kumar, P.,Sharma, A.K. (登録日: 2021-12-01, 公開日: 2022-07-27, 最終更新日: 2023-11-29)

主引用文献

Kumar, R.,Das, J.,Mahto, J.K.,Sharma, M.,Vivek, S.,Kumar, P.,Sharma, A.K.
Crystal structure and molecular characterization of NADP + -farnesol dehydrogenase from cotton bollworm, Helicoverpaarmigera.
Insect Biochem.Mol.Biol., 147:103812-103812, 2022

PubMed Abstract: Farnesol dehydrogenase (FDL) orchestrates the oxidation reaction catalyzing farnesol to farnesal, a key step in the juvenile hormone (JH) biosynthesis pathway of insects and hence, represents a lucrative target for developing insect growth regulators (IGRs). However, information on the structural and functional characterization of JH-specific farnesol dehydrogenase in insects remains elusive. Herein, we identified a transcript that encodes farnesol dehydrogenase (HaFDL) from Helicoverpa armigera, a major pest of cotton. The investigations of molecular assembly, biochemical analysis and spatio-temporal expression profiling showed that HaFDL exists as a soluble homo-tetrameric form, exhibits a broad substrate affinity and is involved in the JH-specific farnesol oxidation in H. armigera. Additionally, the study presents the first crystal structure of the HaFDL-NADP enzyme complex determined at 1.6 Å resolution. Structural analysis revealed that HaFDL belongs to the NADP-specific cP2 subfamily of the classical short-chain dehydrogenase/reductase (SDR) family and exhibits typical structural features of those enzymes including the conserved nucleotide-binding Rossman-fold. The isothermal titration calorimetry (ITC) showed a high binding affinity (dissociation constant, Kd, 3.43 μM) of NADP to the enzyme. Comparative structural analysis showed a distinct substrate-binding pocket (SBP) loop with a spacious and hydrophobic substrate-binding pocket in HaFDL, consistent with the biochemically observed promiscuous substrate specificity. Finally, based on the crystal structure, substrate modeling and structural comparison with homologs, a two-step reaction mechanism is proposed. Overall, the findings significantly impact and contribute to our understanding of farnesol dehydrogenase functional properties in JH biosynthesis in H. armigera.

PubMed: 35820537
DOI: 10.1016/j.ibmb.2022.103812

実験手法

X-RAY DIFFRACTION (1.6 Å)