Porin channels

Porin channels are impHcated in the transport of cephalosporins because ceds deficient in porins are much more impermeable than are ceds that are rich in porins. The porins appear to function as a molecular sieve, adowing molecules of relatively low molecular weight to gain access to the periplasmic space by passive diffusion. In enterobacteria, a clear correlation exists between porin quantity and cephalosporin resistance, suggesting that the outer membrane is the sole barrier to permeabdity. However, such a relationship is not clearly defined for Pseudomonas aeruginosa where additional barriers may be involved (139,144,146). 

Structural basis for sugar translocation through malto-porin channels at 3.1 A resolution. Science 267 512-514, 1995. 

The amino acid compositions and sequences of the /3-strands in porin proteins are novel. Polar and nonpolar residues alternate along the /3-strands, with polar residues facing the central pore or cavity of the barrel and nonpolar residues facing out from the barrel where they can interact with the hydrophobic lipid milieu of the membrane. The smallest diameter of the porin channel is about 5 A. Thus, a maltodextrin polymer (composed of two or more glucose units) must pass through the porin in an extended conformation (like a spaghetti strand). 

Source Adapted, from Benz, R., 1984. Sti ucture and selecdvity of porin channels. Current Topics in Membrane TrawsjiJorf 21 199-219 and Benz, R., 1988. Sti ucture and function of porins from Gram-negative bacteria. Annual Review of Microbiology 42 359-393. 

In Gram-negative bacteria, diffusion of (3-lactam antibiotics into the periplasm (where the activity of PBPs takes place) occurs via the channels that porins create in the outer membrane. The number and properties of the porin molecules are such that diffusion is relatively rapid in E. coli but much slower in Enterobacter and Pseudomonas. Mutants can be selected after the permeability of porin channels or their number has been decreased. A slow diffusion into... 

Schirmer, T., and Phale, P. S. (1999). Brownian dynamics simulation of ion flow through porin channels./ Mol. Biol. 294, 1159-1167. 

Fluoroquinolones must penetrate bacteria to reach their target, DNA gyrase. The second mechanism of fluoroquinolone resistance is decreased cell wall permeability. The fluoroquinolones diffuse through porin channels in the outer membrane of Gram-negative bacteria. Mutation results in a decrease in porin channel proteins, resulting in decreased uptake of the fluoroquinolones into bacterial cells. Alterations in a wide range of outer membrane proteins in Pseudomonas spp. result in resistance. From these mutations, the increase in MIC of the fluoroquinolones is relatively low (2-to 32-fold). Flowever, there is cross-resistance with unrelated antibiotics, most frequently cefoxitin, chloramphenicol, trimethoprim and tetracycline. 

The hydrated nature of amino acid residues lining the porin channels presents an energetically unfavourable barrier to the passage of hydrophobic molecules. In rough strains, the reduction in the amount of polysaccharide on the cell surface allows hydrophobic molecules to approach more closely the surface of the outer membrane and cross the outer membrane lipid bilayer by passive diffusion. This process is greatly facilitated in deep rough and heptose-less strains which have phospholipid molecules on the outer face of their outer membranes as well as on the inner face. The exposed areas of phospholipids favour the absorption and penetration of the hydrophobic agents. 

Figure 3 The OmpF porin channel (left) emhedded in an explicit POPC membrane, and (right) the corresponding top view of the OmpF. The L3 loop in the constriction zone of the three monomers is represented by the large shaded cylinder. The structure has been obtained from the protein database (lompf.pdb) and the plot has been rendered with...

Electrostatic Properties of Two Porin Channels from Escherichia Coli. 

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