10.1021/acsinfecdis.8b00149.s001
Susruta Samanta
Susruta
Samanta
Igor Bodrenko
Igor
Bodrenko
Silvia Acosta-Gutiérrez
Silvia
Acosta-Gutiérrez
Tommaso D’Agostino
Tommaso
D’Agostino
Monisha Pathania
Monisha
Pathania
Ishan Ghai
Ishan
Ghai
Christian Schleberger
Christian
Schleberger
Dirk Bumann
Dirk
Bumann
Richard Wagner
Richard
Wagner
Mathias Winterhalter
Mathias
Winterhalter
Bert van den Berg
Bert
van den Berg
Matteo Ceccarelli
Matteo
Ceccarelli
Getting Drugs through Small Pores: Exploiting the
Porins Pathway in <i>Pseudomonas aeruginosa</i>
American Chemical Society
2018
antibiotic
bacteria
ceftazidime
OccK 8 pore
Pseudomonas aeruginosa
substrate
translocation
Outer membrane proteomics
2018-07-24 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Getting_Drugs_through_Small_Pores_Exploiting_the_Porins_Pathway_in_i_Pseudomonas_aeruginosa_i_/6946055
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 <i>Pseudomonas aeruginosa</i>. The high-resolution
X-ray structure and electrophysiology highlighted a very narrow pore.
However, experimental <i>in vitro</i> 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.