Computational Study Reveals the Molecular Mechanism of the Interaction between the Efflux Inhibitor PAβN and the AdeB Transporter from Acinetobacter baumannii
Abstract
Phenylalanine-arginine β-naphthylamide (PAβN) is a broad-spectrum efflux pump inhibitor that has shown to potentiate the activity of antibiotics in Gram-negative bacteria. AdeB is a part of the AdeABC tripartite pump that plays a pivotal role in conferring efflux-mediated resistance in Acinetobacter baumannii. To understand the molecular mechanism of efflux pump inhibition by PAβN, we investigated the interaction of PAβN with AdeB using different computational methods. We observed that PAβN does not have specific binding interactions with the proximal binding site and interacts strongly with the distal binding pocket. The Phe loop located between the proximal and distal binding pockets plays a key role in the PAβN-mediated inhibition and acts as a gate between the binding pockets. Molecular dynamics simulations suggested that PAβN behaved like a climber as we observed switching of the interaction energies between the ligand and the key Phe residues of the binding site during the course of the simulation. PAβN uses the hydrophobic microenvironment formed by Phe residues in the distal binding pocket to keep the binding monomer in the binding conformation. The simulation data suggests that this binding event should result in the i...Continue Reading
References
Effect of efflux pump inhibitors on bile resistance and in vivo colonization of Campylobacter jejuni
Citations
RND efflux pumps in Gram-negative bacteria; regulation, structure and role in antibiotic resistance.
Software Mentioned
Related Concepts
Related Feeds
Antifungals (ASM)
An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.
Acinetobacter Infections
Acinetobacter infections have become common in hospitalized patients, especially in the intensive care unit setting and are difficult to treat due to their propensity to develop antimicrobial drug resistance. Discover the latest research on Acinetobacter Infections here.
Antifungals
An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.