Investigations on the Interactions of λPhage-Derived Peptides Against the SrtA Mechanism in Bacillus anthracis

Abstract

Bacillus anthracis is a well-known bioweapon pathogen, which coordinates the expression of its virulence factors in response to a specific environmental signal by its protein architecture. Absences of sortase signal functioning may fail to assemble the surface linked proteins and so B. anthracis cannot sustain an infection with host cells. Targeting the signaling mechanism of B. anthracis can be achieved by inhibition of SrtA enzyme through λphage-derived plyG. The lysin enzyme plyG is experimentally proven as bacteriolytic agent, specifically kill's B. anthracis by inhibiting the SrtA. Here, we have screened the peptides from λphage lysin, and these peptides are having the ability as LPXTG competitive inhibitors. In comparison to the activator peptide LPXTG binding motif, λphage lysin based inhibitor peptides are having much supremacy towards binding of SrtA. Finally, peptide structures extracted from PlyG are free from toxic, allergic abilities and also have the ability to terminate the signal transduction mechanism in B. anthracis.

Molecular insights of protein contour recognition with ligand pharmacophoric sites through combinatorial library design and MD simulation in validating HTLV-1 PR inhibitors

“…The GROMACS program package (http://www.gromacs.org) adopting the OPLS-AA force field parameters was used for energy minimization and MD simulations. 49,50 Additionally, MD simulations were performed for the ligand bound docked structures of HTLV-1 PR, which were the outcome of combinatorial library design and free energy analysis. 48 The total simulation was performed in the NPT ensemble at constant temperature (300 K) and pressure (1 bar), with a time step of 2 fs.…”

Sortagging: A Robust and Efficient Chemoenzymatic Ligation Strategy

“…Due to their central role in virulence, sortases are promising targets for the treatment and prevention of infections caused by Gram‐positive bacteria. Inhibitors of the transpeptidases are, for example, aaptamines,21 curcumin,22 phosphinic peptidomimetics23 or peptidyl‐diazomethane and peptidyl‐chloromethane derivatives24 in the case of SrtA from S. aureus and Streptococcus mutants, or the lysine enzyme plyG and plyG based peptides in the case of SrtA from B. anthracis 25…”

“…Inhibitors of the transpeptidases are, for example, aaptamines, [21] curcumin, [22] phosphinic peptidomimetics [23] or peptidyl-diazomethane and peptidyl-chloromethane derivatives [24] in the case of SrtA from S. aureus and Streptococcus mutants, or the lysine enzyme plyG and plyG based peptides in the case of SrtA from B. anthracis. [25] Figure 1. A) Schematic representation of sortase A-mediated transpeptidation.…”

Targeting the cyclin-binding groove site to inhibit the catalytic activity of CDK2/cyclin A complex using p27KIP1-derived peptidomimetic inhibitors

“…The complete geometry optimization was performed using hybrid DFT with B3LYP. Optimization process was performed in an aqueous environment using the Poisson-Boltzmann solvent so as to simulate physiological conditions [42]. All the peptidomimetic inhibitors were minimized by quantum mechanical (QM) methods applied by Jaguar suite.…”

“…The QM methods of optimization were performed to obtain the global minimum energy conformation of known penta peptide inhibitor and peptidomimetics. Generating the least energy conformation of peptides or peptidomimetics is a very essential task to predict the bioactive conformation, which is associated with the receptor binding mechanism [42]. In terms of optimization, the least energy conformers of peptidomimetics were chosen for preliminary fragment-based toxicity prediction using OSIRIS toxicity tool.…”