FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2951093043> ?p ?o ?g. }

• W2951093043 endingPage "845" @default.
• W2951093043 startingPage "836" @default.
• W2951093043 abstract "Efflux pumps of the Resistance-Nodulation-cell Division superfamily confer multi-drug resistance to Gram-negative bacteria. The most-studied polyspecific transporter belonging to this class is the inner-membrane trimeric antiporter AcrB of Escherichia coli. In previous studies, a functional rotation mechanism was proposed for its functioning, according to which the three monomers undergo concerted conformational changes facilitating the extrusion of substrates. However, the molecular determinants and the energetics of this mechanism still remain unknown, so its feasibility must be proven mechanistically.A computational protocol able to mimic the functional rotation mechanism in AcrB was developed. By using multi-bias molecular dynamics simulations we characterized the translocation of the substrate doxorubicin driven by conformational changes of the protein. In addition, we estimated for the first time the free energy profile associated to this process.We provided a molecular view of the process in agreement with experimental data. Moreover, we showed that the conformational changes occurring in AcrB enable the formation of a layer of structured waters on the internal surface of the transport channel. This water layer, in turn, allows for a fairly constant hydration of the substrate, facilitating its diffusion over a smooth free energy profile.Our findings reveal a new molecular mechanism of polyspecific transport whereby water contributes by screening potentially strong substrate-protein interactions.We provided a mechanistic understanding of a fundamental process related to multi-drug transport. Our results can help rationalizing the behavior of other polyspecific transporters and designing compounds avoiding extrusion or inhibitors of efflux pumps." @default.
• W2951093043 created "2019-06-27" @default.
• W2951093043 creator A5000189011 @default.
• W2951093043 creator A5030274286 @default.
• W2951093043 creator A5031949142 @default.
• W2951093043 creator A5040786040 @default.
• W2951093043 creator A5059598818 @default.
• W2951093043 creator A5084434615 @default.
• W2951093043 date "2018-04-01" @default.
• W2951093043 modified "2023-10-02" @default.
• W2951093043 title "Water-mediated interactions enable smooth substrate transport in a bacterial efflux pump" @default.
• W2951093043 cites W1606713343 @default.
• W2951093043 cites W1806547840 @default.
• W2951093043 cites W1948806874 @default.
• W2951093043 cites W1968140197 @default.
• W2951093043 cites W1968759341 @default.
• W2951093043 cites W1969723894 @default.
• W2951093043 cites W1975874401 @default.
• W2951093043 cites W1976499671 @default.
• W2951093043 cites W1978012161 @default.
• W2951093043 cites W1978159078 @default.
• W2951093043 cites W1981225934 @default.
• W2951093043 cites W1983806833 @default.
• W2951093043 cites W1985400607 @default.
• W2951093043 cites W1986473204 @default.
• W2951093043 cites W1988149100 @default.
• W2951093043 cites W1988715261 @default.
• W2951093043 cites W1988972583 @default.
• W2951093043 cites W1991465840 @default.
• W2951093043 cites W1993177346 @default.
• W2951093043 cites W1997234523 @default.
• W2951093043 cites W1997477098 @default.
• W2951093043 cites W1999979510 @default.
• W2951093043 cites W2003186950 @default.
• W2951093043 cites W2003240840 @default.
• W2951093043 cites W2009089119 @default.
• W2951093043 cites W2029667189 @default.
• W2951093043 cites W2036964949 @default.
• W2951093043 cites W2041308144 @default.
• W2951093043 cites W2042527516 @default.
• W2951093043 cites W2042669181 @default.
• W2951093043 cites W2049862828 @default.
• W2951093043 cites W2054248955 @default.
• W2951093043 cites W2065652119 @default.
• W2951093043 cites W2070196678 @default.
• W2951093043 cites W2071083537 @default.
• W2951093043 cites W2073623394 @default.
• W2951093043 cites W2075316331 @default.
• W2951093043 cites W2079685391 @default.
• W2951093043 cites W2082383598 @default.
• W2951093043 cites W2083308932 @default.
• W2951093043 cites W2083669034 @default.
• W2951093043 cites W2085943043 @default.
• W2951093043 cites W2086941118 @default.
• W2951093043 cites W2088095424 @default.
• W2951093043 cites W2091127706 @default.
• W2951093043 cites W2101470639 @default.
• W2951093043 cites W2103185849 @default.
• W2951093043 cites W2112154906 @default.
• W2951093043 cites W2132019100 @default.
• W2951093043 cites W2132067013 @default.
• W2951093043 cites W2142318169 @default.
• W2951093043 cites W2142400495 @default.
• W2951093043 cites W2147993766 @default.
• W2951093043 cites W2150981663 @default.
• W2951093043 cites W2153280156 @default.
• W2951093043 cites W2153601116 @default.
• W2951093043 cites W2159913597 @default.
• W2951093043 cites W2267817589 @default.
• W2951093043 cites W2274347034 @default.
• W2951093043 cites W2275283872 @default.
• W2951093043 cites W2276330190 @default.
• W2951093043 cites W2298100294 @default.
• W2951093043 cites W2300011769 @default.
• W2951093043 cites W2328752440 @default.
• W2951093043 cites W2334194304 @default.
• W2951093043 cites W2404280981 @default.
• W2951093043 cites W2415634955 @default.
• W2951093043 cites W2474075311 @default.
• W2951093043 cites W2537310711 @default.
• W2951093043 cites W2549286116 @default.
• W2951093043 cites W2566037451 @default.
• W2951093043 cites W2594737520 @default.
• W2951093043 cites W2743848994 @default.
• W2951093043 cites W2745506379 @default.
• W2951093043 doi "https://doi.org/10.1016/j.bbagen.2018.01.010" @default.
• W2951093043 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29339082" @default.
• W2951093043 hasPublicationYear "2018" @default.
• W2951093043 type Work @default.
• W2951093043 sameAs 2951093043 @default.
• W2951093043 citedByCount "41" @default.
• W2951093043 countsByYear W29510930432018 @default.
• W2951093043 countsByYear W29510930432019 @default.
• W2951093043 countsByYear W29510930432020 @default.
• W2951093043 countsByYear W29510930432021 @default.
• W2951093043 countsByYear W29510930432022 @default.
• W2951093043 countsByYear W29510930432023 @default.
• W2951093043 crossrefType "journal-article" @default.

• next