In silico Binding Profile Analysis and In vitro Investigation on Chitin Synthase Substrate and Inhibitors from Maize Stem Borer, Chilo partellus

Title:In silico Binding Profile Analysis and In vitro Investigation on Chitin Synthase Substrate and Inhibitors from Maize Stem Borer, Chilo partellus

Volume: 17 Issue: 7

Author(s): Sampathkumar Ranganathan, Dinakara Rao Ampasala*, Bhagath Kumar Palaka, Anbumani Velmurugan Ilavarasi, Ishwar Patidar, Lakshmi Priya Poovadan and Tuleshwori Devi Sapam

Affiliation:

• Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Pondicherry 605014, India

Keywords: Chitin synthase A, Chilo partellus, molecular docking, molecular dynamics, UDP-GlcNAc, Nikkomycin Z and polyoxins.

Abstract: Introduction: Insect growth and metamorphosis are strictly dependent on the structural changes that occur in chitin containing tissues and organs. Chitin synthase catalyzes chitin polymerization by β-(1, 4) glycosidic linkage of N-acetyl-D-glucosamine (GlcNAc) monomers; the major component of insect cuticles. Targeting this enzyme could be a promising strategy to control insect pests while avoiding adverse effects on coexisting populations. Nikkomycin Z and polyoxins are commercially available fungal inhibitors known to bind to the nucleotide-binding sites of insects and fungal chitin synthase. But the binding mode of chitin synthase has not been explored to date as its structure is not available yet.

Methods: To understand the structural features of the Chilo partellus chitin synthase enzyme (CpCHS), the three-dimensional (3D) structure of the CpCHS catalytic domain was modeled using ROBETTA webserver. The obtained model was used to investigate the binding mode of its substrate, uridine diphosphate-N-acetyl-D-glucosamine (UDP-GlcNAc), and inhibitors (nikkomycin Z and polyoxins) by molecular docking approach using Schrödinger Suite-Maestro v9.2. The docked complexes were further investigated for their interaction stability by performing molecular dynamics (MD) simulations using GROMACS v5.1.2.

Results: Our study highlighted the significance of various interactions made by CHS residues present in the Walker-B loop and donor-binding motifs with the substrate (UDP-GlcNAc), and GEDR motif with an acceptor (GlcNAc). Also, the interactions of the QRRRW motif while forming chitin polymer were explored. We observed that the inhibitors exhibited good binding affinity with these motifs, indicated by their docking and binding affinity scores.

Conclusion: In vitro analysis suggested that nikkomycin Z showed higher inhibition of chitin synthase activity at a concentration of 2.5 μg.L^-1. Our study provided insights into the crucial interactions of chitin synthase while designing inhibitors against insect pests.

Cite this article as:

Ranganathan Sampathkumar, Ampasala Rao Dinakara*, Palaka Kumar Bhagath, Ilavarasi Velmurugan Anbumani, Patidar Ishwar, Poovadan Priya Lakshmi and Sapam Devi Tuleshwori, In silico Binding Profile Analysis and In vitro Investigation on Chitin Synthase Substrate and Inhibitors from Maize Stem Borer, Chilo partellus, Current Computer-Aided Drug Design 2021; 17 (7) . https://dx.doi.org/10.2174/1573409916666201013150920

DOI https://dx.doi.org/10.2174/1573409916666201013150920	Print ISSN 1573-4099
Publisher Name Bentham Science Publisher	Online ISSN 1875-6697