Molecular Docking and Binding Study of the LytA Enzyme with the sodium deoxycholate Substrate

Background and Objectives: The LytA protein is one of the main autolysins in the Streptococcus pneumoniae with the N-acetylmuramoyl-l-alanine amidase activity. Lyt A autolysis occurred by degrading the lactyl-amido bond between the glycan strand of the peptidoglycan and stem peptide. It has been shown that the all of pneumococci lyse when they grow in the presence of sodium deoxycholate as a bile salt due to stimulation of the amidase enzymes for example LytA. In this study, we report for the first time the interaction between the lytA as protein and deoxycholate as ligand. Materials and Methods: The X-ray crystal structure of Lyt A as protein and deoxycholate as ligand were retrieved and energetically minimized by Molegro Molecular Viewer. The binding site and surface of enzymes were detected. In addition, the docking studies were performed by Molegro 2.5 using Moldock algorithm. Finally, the number of H bonds and electrostatic energies for each pose were calculated. Results: In the present study, a structural approach taken to consider the mode by which the main pneumococcal autolysin Lyt A interacts with the deoxycholat substrate. Our results demonstrate that LytA has five binding sites for interaction with the deoxycholate substrate. In results, two binding sites were predicted (binding sites 3 and 5) in the amino-terminal domain; it seems that these two regions are likely to have interacted with the deoxycholate substrate. Moreover, the capacity to induce autolysis was considered as the role of the N-terminal amidase. Conclusion: The interaction of the main pneumococcal autolysin (LytA) with the deoxycholate substrate have been investigated by using Molegro. There are 13 amino acid residues (Ser27, Thr28, Pro47, Phe51, Gly65, Trp72, Asp73, Asn79, His133, Thr137, His147, Val148, Asp149) in active site of S. pneumonie which interacted with chemical ions. The analyzed results suggest that the domain 5 of LytA binds with the deoxycholate, which had these residues The data presented here reveal five binding sites, which along with multiple residues in all five regions are involved in substrate recognition.