Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.01.03.522678v1?rss=1
Authors: Shakibaie, M. R., Modarresi, F., Azizi, O., Tadjrobehkar, O., Ghaemi, M. M.
Abstract:
No report exists on the role of Mastoparan B (MP-B) as an RND efflux pump inhibitor in multi-drug resistant (MDR) Acinetobacter baumannii. Here, we performed a series of in-silico experiments to predict the inhibition of the AdeB efflux pump by MP-B as a drug target agent. For this reason, an MDR strain of A. baumannii was subjected to MICs against 12 antibiotics and MP-B. Expression of the adeB gene in the presence and absence of sub-MIC of MP-B was studied by qRT-PCR. It was found that MP-B had potent antimicrobial activity (MIC=1 g/ml) associated with a 20-fold decrease in the adeB gene expression at the sub-MIC level. The 3D analyses using several automated servers confirmed that the AdeB protein is an inner membrane of the RND tripartite complex system with helix-turn-helix conformation and a pore rich in Phe, Ala, and Lys residue. Furthermore, 20 ligands were generated from the initial docked poses to create the correct protein-peptide complexes using the BioLiP pipeline. The pose showed high Z=1.2, C=1.41, TM=0.99, and RMSD=4.4 scores selected for docking purposes. The molecular docking via AutoDock/Vina revealed that MP-B form H-bound by Val 499, Phe 454, Thr 474, Ser 461, Gly 465, and Tyr 468 residues of the AdeB helix-5 and caused a shift in the dihedral angle ({Phi}/{psi}) by distances of 9.0 [A], 9.3 [A], and 9.6 [A], respectively. This shift in folding was detected by AlphaFold 2 and influenced the overall druggability of the protein.
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