Binding protein dependent secondary transporters

Jacobs, M. H., van der Heide, T., Driessen, A. J. and Konings, W. N. (1996). Glutamate transport in Rhodobacter sphaeroides is mediated by a novel binding protein-dependent secondary transport system, Proc. Natl Acad. Sci. USA, 93, 12 786-12 790. 

Gram-positive lactic acid bacteria possess several MDRs that excrete out of the cell a wide variety of mainly cationic lipophilic cytotoxic compotmds as well as many clinically relevant antibiotics. These MDRs are either proton/drug antiporters belonging to the major facilitator superfamily of secondary transporters or ATP-dependent primary transporters belonging to the ATP-binding cassette superfamily of transport proteins. 

Retinol is nearly always present in the food in the form of esters which are hydrolysed in the lumen of the intestine. The retinol released is quite readily absorbed into the mucosal cells where it is re-esterified, chiefly with palmitic acid. The retinyl esters are then transported via the lymphatic system into the portal circulation from which they are removed and stored in the liver. Release of the vitamin from the liver depends on the production by the liver of a special retinolbinding protein (RBP). Production of the retinol-binding protein may be disturbed in diseases of the liver or kidneys or in protein/energy malnutrition. In such circumstances retinol cannot be mobilized from the stores and a secondary deficiency may result. Thus it can be seen that the level of retinol in the general circulation is normally highly regulated and is more or less independent of the body s reserves. 

This tertiary structure of a protein is extraordinarily important because it determines the shape of these huge molecules and biological activity depends intimately on these shapes. Evolution has produced proteins that have pockets into which specific molecules called substrates fit. This enzyme-substrate binding allows for the proper orientation for reaction of the substrate. The reaction could be complicated, or as simple as the hydrolysis of an ester. In other molecules, substrates are bound only for transportation purposes. These binding sites are a direct consequence of the primary structure that determines the secondary and tertiary structures. Figure 23.25 gives a schematic representation of this process. 

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