7w61

Publication Abstract from PubMed

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 A 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 muM) 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.

Crystal structure and molecular characterization of NADP(+)-farnesol dehydrogenase from cotton bollworm, Helicoverpaarmigera.,Kumar R, Das J, Mahto JK, Sharma M, Vivek S, Kumar P, Sharma AK Insect Biochem Mol Biol. 2022 Jul 9;147:103812. doi: 10.1016/j.ibmb.2022.103812. PMID:35820537^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.