Journal Article

Computational Modelling, Functional Characterization and Molecular Docking to Lead Compounds of Bordetella pertussis Diaminopimelate Epimerase

Singh, Shilpy, Praveen, Afsana, Khanna, Suruchi M

2023

Overview

Bordetella pertussis, the causative agent of whooping cough, is an opportunistic virulent bacterial pathogen that is resistant to a wide range of antibiotics due to a variety of resistance mechanisms. Looking at the increasing number of infections caused by B. pertussis and its resistance to diverse antibiotics, it is essential to develop alternative strategies to fight against B. pertussis. Diaminopimelate epimerase (DapF) is an important enzyme of the lysine biosynthesis pathway in B. pertussis that catalyzes the formation of meso-2, 6-diaminoheptanedioate (meso-DAP), which is an important step in lysine metabolism. Therefore, Bordetella pertussis diaminopimelate epimerase (DapF) becomes an ideal target for antimicrobial drug development. In the present study, computational modelling, functional characterization, binding studies, and docking studies of BpDapF with lead compounds were carried out using different in silico tools. In silico prediction results in the secondary structure, 3-D structure analysis, and protein-protein interaction analysis of BpDapF. Docking studies further showed the respective amino acid residues for ligands in the phosphate‑binding loop of BpDapF play a vital role in the formation of H‑bonds with these ligands. The site where the ligand was bound is a deep groove, which is regarded as the binding cavity of the protein. Biochemical studies indicated that Limonin (binding energy − 8.8 kcal/mol), Ajmalicine (binding energy − 8.7 kcal/mol), Clinafloxacin (binding energy − 8.3 kcal/mol), Dexamethasone (binding energy − 8.2 kcal/mol), and Tetracycline (binding energy − 8.1 kcal/mol) exhibited promising binding towards the drug target DapF of B. pertussis in comparison with the binding between other drugs and act as the potential inhibitors of BpDapF that eventually can reduce the catalytic activity of BpDapF.

• Publisher: Springer Nature B.V
• Subject: Ajmalicine / Amino acids / Antibiotics / Antimicrobial agents / Binding energy / Biosynthesis / Bordetella pertussis / Catalytic activity / Clinafloxacin / Computer applications / Dexamethasone / Diaminopimelate epimerase / Drug development / Energy / Epimerase / Grooves / Heat treating / Lead compounds / Ligands / Lysine / Molecular docking / Opportunist infection / Pertussis / Protein interaction / Protein structure / Proteins / Secondary structure / Structural analysis / Therapeutic targets / Thermodynamics / Whooping cough