http://www.cnr.it/ontology/cnr/individuo/prodotto/ID1353

Interaction of zwitterionic penicillins with the OmpF channel facilitates their translocation (Articolo in rivista)

Type

Prodotto della ricerca (Classe)
Articolo in rivista (Classe)

Label

Interaction of zwitterionic penicillins with the OmpF channel facilitates their translocation (Articolo in rivista) (literal)

Anno

2006-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1529/biophysj.105.075192 (literal)

Alternative label

Danelon, C; Nestorovich, EM; Winterhalter, M; Ceccarelli, M; Bezrukov, SM (2006)
Interaction of zwitterionic penicillins with the OmpF channel facilitates their translocation
in Biophysical journal (Print)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Danelon, C; Nestorovich, EM; Winterhalter, M; Ceccarelli, M; Bezrukov, SM (literal)

Pagina inizio

1617 (literal)

Pagina fine

1627 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

90 (literal)

Rivista

Biophysical journal (Rivista)

Note

ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA; Inst Pharmacol & Biol Struct, Toulouse, France; Int Univ Bremen, Bremen, Germany; Univ Cagliari, Dept Phys, I-09042 Monserrato, Italy; Univ Cagliari, Sardinian Lab Computat Mat Sci, I-09042 Monserrato, Italy (literal)

Titolo

Interaction of zwitterionic penicillins with the OmpF channel facilitates their translocation (literal)

Abstract

To study translocation of beta-lactam antibiotics of different size and charge across the outer bacterial membrane, we combine an analysis of ion currents through single trimeric outer membrane protein F ( OmpF) porins in planar lipid bilayers with molecular dynamics simulations. Because the size of penicillin molecules is close to the size of the narrowest part of the OmpF pore, penicillins occlude the pore during their translocation. Favorably interacting penicillins cause time-resolvable transient blockages of the small-ion current through the channel and thereby provide information about their dynamics within the pore. Analyzing these random fluctuations, we find that ampicillin and amoxicillin have a relatively high affinity for OmpF. In contrast, no or only a weak interaction is detected for carbenicillin, azlocillin, and piperacillin. Molecular dynamics simulations suggest a possible pathway of these drugs through the OmpF channel and rationalize our experimental findings. For zwitterionic ampicillin and amoxicillin, we identify a region of binding sites near the narrowest part of the channel pore. Interactions with these sites partially compensate for the entropic cost of drug confinement by the channel. Whereas azlocillin and piperacillin are clearly too big to pass through the channel constriction, dianionic carbenicillin does not find an efficient binding region in the constriction zone. Carbenicillin's favorable interactions are limited to the extracellular vestibule. These observations confirm our earlier suggestion that a set of high-affinity sites at the narrowest part of the OmpF channel improves a drug's ability to cross the membrane via the pore. (literal)

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