Bacterial membranes function

A few well-controlled clinical studies suggested a potential plaque-inhibiting effect for dentifrices containing staimous fluoride. However, these results were most likely due to the stannous ion rather than to fluoride the positive charge of the stannous ion may interfere with bacterial membrane function, bacterial adhesion, and glucose uptake, thereby inhibiting the formation of plaque. 

The lipid bilayer forms a barrier to transport of matter into and out of the cell. This barrier function is essential since cells need to be able to control their internal milieu, regardless of the external environment. (Some antibiotics work by disrnpting the barrier function of bacterial membranes see Chapter 23). At the same time, some communication of signals and materials across the bilayer must occur. Special mechanisms to do this are a key property of biological membranes. More specifically, these mechanisms are the province of proteins that one finds in these membranes. 

Daptomycin (15 Cubicin ) Daptomycin (15) Lipopeptide NP Microbial Antibacterial Disrupts multiple aspects of bacterial cell membrane function 211-225... 

Membranes contain many largely a-helical proteins. Cell surface receptors often appear to have one, two, or several membrane-spanning helices (see Chapter 8). The single peptide chain of the bacterial light-operated ion pump bacteriorhodopsin (Fig. 23-45) folds back upon itself to form seven helical rods just long enough to span the bacterial membrane in which it functions.189 Photosynthetic reaction centers contain an a helix bundle which is formed from two different protein subunits (Fig. 23-31).190 A recently discovered a,a barrel contains 12 helices. Six parallel helices form an inner barrel and 6 helices antiparallel to the first 6 form an outer layer (see Fig. 2-29).191-193... 

In green plants, which contain little or no cholesterol, cydoartenol is the key intermediate in sterol biosynthesis.161-1623 As indicated in Fig. 22-6, step c, cydoartenol can be formed if the proton at C-9 is shifted (as a hydride ion) to displace the methyl group from C-8. A proton is lost from the adjacent methyl group to close the cyclopropane ring. There are still other ways in which squalene is cyclized,162/163/1633 including some that incorporate nitrogen atoms and form alkaloids.1631 One pathway leads to the hop-anoids. These triterpene derivatives function in bacterial membranes, probably much as cholesterol does in our membranes. The three-dimensional structure of a bacterial hopene synthase is known.164 1643 Like glucoamylase (Fig. 2-29) and farnesyl transferase, the enzyme has an (a,a)6-barrel structure in one domain and a somewhat similar barrel in a second domain. 

Bacterial membranes have a much more complex construction than mammalian membranes. This enables bacteria to survive in the various environments of host organisms. Knowledge of the composition and functioning of bacterial membranes is therefore essential to the development of anti-infective drugs. In order to be effective, antibacterial agents not only have to have optimal pharmacokinetic properties such as uptake and distribution in the patient, but they must also be able to cross an additional barrier, the cell wall of the bacteria, so that they can reach the target site. This additional barrier is remarkable on account of its rigidity and permeability. The construction and structural uniqueness of this barrier is briefly described below. 

Particularly it became necessary to consider the bacterial membrane. As things stand now, the bacterial cell wall is thought of as an outer skeleton which can be freely traversed by macromolecules and is important for the mechanical structure and protection of the cell. It is made up of polysaccharides and carbohydrate-derived substances, which include some peptide groups. Underneath the cell wall there is the cell membrane, which appears to be the seat of the important physiological functions of assimilation and excretion. Some findings suggest... 

Among the outer membrane enzymes, OmpT is a special protease that has been implicated in the pathogenicity of bacteria. It is monomeric with the active center pointing to the outside (Vandeputte-Rutten et al., 2001). Another enzyme, the phospholipase A OmpLA, produces holes in the outer membrane when it is activated. The activation process has not yet been clarified, but it is known to require a dimerization of OmpLA in the membrane. The activation by dimer formation has been verified by a crystal structure analysis of an OmpLA dimer that was produced by a reaction with an inhibitor (Snijder et al., 1999). It showed that each active center contained a catalytic triad Ser-His-Asn on one subunit and an ox-anion hole formed by an amide together with a hydrated Ca2+ ion on the other. The active centers are well placed for deacylating lipopolysaccha-rides of the external leaflet of the outer bacterial membrane. OmpLA functions in the secretion of colicins and virulence factors. 

Nicotinamide nucleotide transhydrogenases may be divided into two classes. One class is present in certain bacteria, and possibly in some plants, is an easily extractable, water-soluble enzyme is not functionally linked to the energy-transfer system of the bacterial membrane is a fiavoprotein and is specific for the 4B-hydrogen atom of both NADH and NADPH. The other class is present in both certain bacteria and in mitochondria is a firmly membrane-bound water-insoluble enzyme is functionally linked to the energy-transfer system of the bacterial or mitochondrial membrane is not known to be a flavoprotein and is specific for the 4A-hydrogen atom of NADH and the 4B-hydrogen atom of NADPH. For the sake of convenience, the two classes of enzyme will be referred to below as BB-specific and AB-specific transhydrogenases, respectively. 

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