Hydrogen peroxide and hypochlorous acid influx through the major S. Typhimurium porin OmpD is affected by substitution of key residues of the channel

被引:15
作者
Aguayo, Daniel [2 ,4 ]
Pacheco, Nicolas [1 ]
Morales, Eduardo H. [3 ]
Collao, Bernardo [1 ]
Luraschi, Roberto [1 ]
Cabezas, Carolina [1 ]
Calderon, Paulina [1 ]
Gonzalez-Nilo, Fernando [2 ,4 ]
Gil, Fernando [1 ]
Calderon, Ivan L. [1 ]
Saavedra, Claudia P. [1 ]
机构
[1] Univ Andres Bello, Fac Ciencias Biol, Dept Ciencias Biol, Lab Microbiol Mol, Santiago, Chile
[2] Univ Andres Bello, Fac Ciencias Biol, Ctr Bioinformat & Integrat Biol, Santiago, Chile
[3] Univ Santiago Chile, Fac Quim & Biol, Dept Biol, Lab Microbiol Mol, Santiago, Chile
[4] Univ Valparaiso, Fac Ciencias, Ctr Interdisciplinario Neurociencia Valparaiso, Valparaiso 2366103, Chile
关键词
OmpD porin; Hydrogen peroxide; Hypochlorous acid; Homology modeling; Molecular simulations; MOLECULAR-DYNAMICS SIMULATION; ESCHERICHIA-COLI; SALMONELLA-ENTERICA; MEMBRANE-PROTEIN; GENE; PERMEABILITY; SELECTIVITY; SYSTEMS; EFFLUX; REGION;
D O I
10.1016/j.abb.2015.01.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
OmpD is the major Salmonella enterica serovar Typhimurium (S. Typhimurium) porin and mediates hydrogen peroxide (H2O2) influx. The results described herein extend this finding to hypochlorous acid (HOCI), another reactive oxygen species that is also part of the oxidative burst generated by the phagosome. S. Typhimurium cells lacking OmpD show decreased HOCI influx, and OmpD-reconstituted proteoliposomes show an increase in the uptake of the toxic compound. To understand this physiologically relevant process, we investigated the role of key OmpD residues in H2O2 and NaOCl transport. Using a theoretical approach, residue K16 was defined as a major contributor to the channel electrostatic properties, and E1 II was shown to directly participate in the size-exclusion limit of the channel. Together, we provide theoretical, genetic, and biochemical evidence that OmpD mediates H2O2 and NaOCl uptake, and that key residues of the channel are implicated in this process. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:38 / 45
页数:8
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