Abstract:
:Understanding molecular properties of outer membrane channels of Gram-negative bacteria is of fundamental significance as they are the entry point of polar antibiotics into bacteria. Outer membrane proteomics revealed OccK8 (OprE) to be among the five most expressed substrate specific channels of the clinically important Pseudomonas aeruginosa. The high-resolution X-ray structure and electrophysiology highlighted a very narrow pore. However, experimental in vitro methods showed the transport of natural amino acids and antibiotics, among them ceftazidime. We used molecular dynamics simulations to reveal the importance of the physicochemical properties of ceftazidime in modulating the translocation through OccK8, proposing a structure-function relationship. As in general porins, the internal electric field favors the translocation of polar molecules by gainful energy compensation in the central constriction region. Importantly, the comparatively narrow OccK8 pore can undergo a substrate-induced expansion to accommodate relatively large-sized substrates.
journal_name
ACS Infect Disjournal_title
ACS infectious diseasesauthors
Samanta S,Bodrenko I,Acosta-Gutiérrez S,D'Agostino T,Pathania M,Ghai I,Schleberger C,Bumann D,Wagner R,Winterhalter M,van den Berg B,Ceccarelli Mdoi
10.1021/acsinfecdis.8b00149subject
Has Abstractpub_date
2018-10-12 00:00:00pages
1519-1528issue
10issn
2373-8227journal_volume
4pub_type
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