7W61

Crystal structure of farnesol dehydrogenase from Helicoverpa armigera

Summary for 7W61

• Entry DOI: 10.2210/pdb7w61/pdb
• Descriptor: Farnesol dehydrogenase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ACETATE ION, ... (7 entities in total)
• Functional Keywords: short chain dehydrogenase, oxidoreductase
• Biological source: Helicoverpa armigera
• Total number of polymer chains: 1
• Total formula weight: 27587.00

Authors

Kumar, R.,Das, J.,Mahto, J.K.,Sharma, M.,Kumar, P.,Sharma, A.K. (deposition date: 2021-12-01, release date: 2022-07-27, Last modification date: 2023-11-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.6 Å)