Pharmacodynamics Studies of Elucidated Bioactive Molecules from Metabolites of Streptomyces longisporoflavus Targeted against γ- Glutamyltranspeptidase (CapD enzyme) of Bacillus anthracis

Inhibition of the γ-Glutamyltranspeptidase (CapD enzyme) has become a promising approach for creating potential antimicrobial drugs to combat B. anthracis. By targeting CapD, it is possible to interfere with the bacterium's potential to produce spores and initiate infection. The high-resolution X-ray crystal structures of the Bacillus anthracis transpeptidase enzyme CapD (PDB code: 3GA9 at a resolution of 2.30Å) were obtained from the Protein Data Bank (PDB). The generated coordinates were subsequently prepared for docking studies using the BIOVIA Discovery Studio Visualizer 2020. The bioactive compounds were identified from the metabolites of S. longisporoflavus. The canonical SMILES of the identified molecules were obtained from PubChem, and in-silico ADME screening and drug-likeness evaluation were conducted using the SwissADME free web application. The ligands and that of the standard medication (Penicillin) were prepared for docking studies with the CapD enzyme using PyRx. This process produced binding models and data on the binding affinity. The models were obtained and the examination of the interaction between the receptor and ligand were visualized using BIOVIA. The ADME study and drug-likeness properties revealed that Butanoic acid hexyl ester and 1, 1-Dibutoxybutane showed close similarities with Penicillin (standard drug), but poor binding affinity with the CapD enzyme. The molecular docking study revealed that Dronabinol, 5-Cholestene-3-ol and Ergost-5-en-3-ol with binding affinity of -7.7,-8.0 and -8.0 have close similarities with Penicillin (-7.4). This study aims to evaluate the therapeutic potential of Streptomyces longisporoflavus bioactive compounds against CapD enzyme of B. anthracis in the face of rising antimicrobial resistance.