ABC transporter

Members of the ATP-binding Cassette (ABC) Superfamily (Davidson and Maloney 2007) belong to 92 currently described families, including 33 families of uptake systems and 59 families of exporters (see TCDB). Each family is, in general, specific for a different type of substrate, although exceptions to this generalization are known. They can be specific for all kinds of small molecules, and members of several families function in the export of macromolecules (proteins, lipids, and complex carbohydrates). They share the charactaistic of being driven by ABC protein-dependent ATP hydrolysis (Davidson and Maloney 2007). 

Over 100,000 sequenced members of the ABC supafamily are collectively available for analysis. They occur in relative numbers of 1 2 3 when aU Uving organisms are considered, but the distributions of these porter types are organism specific. Thus, LAB and actinobacteria display relative proportions of 1 3 2, archaea have 2 3 1, and Gram (-) bacteria and eukaryotes exhibit proportions of 1 2 3 (Table 4.8 and unpublished data). Surprisingly, the distributions of the three topological 

Type/Group ABCl (%) ABC2 (%) ABC3 (%) Proportions Proteins/Organism 

Some of the intestinal transporters that have received most attention in drug discovery and development are undoubtedly the ATP-binding cassette transport proteins and especially ABCB1 (for reviews see Refs [37-39]). There are numerous publications on these transporters, and we are, thus, able to give only a small glance 

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The ABC-transporter superfamily represents a large group of transmembrane proteins. Members of this family are mainly involved in ATP-dependent transport processes across cellular membranes. These proteins are of special interest from a pharmacological point of... 

Most ABC-transporters, especially those located in the plasma membrane, are phosphorylated and glycosylated transmembrane proteins of different molecular weights (e.g., P-gp 170 kDa MRP2 190 kDa BCRP 72 kDa). Topologically, most ABC-transporter show a similar structure they are organized in two transmembrane domains (TMD), each consisting of six... 

ABC Transporters. Figure 1 Structure of ABCB 1, ABCC1, and ABCG2 (NBF nucleotide binding fold TMD transmembrane domaine. Modified according to www.iwaki-kk.co.jp/bio/specialedition/se02.htm). 

Taken together ABC-transporters represent a large family of proteins affecting the pharmacokinetic parameters of various drugs. Here, P-gp is currently the best characterized member and it may also be one of the most important ABC-transporters with regard to drug transport. However, it becomes more and more apparent that ABC-transporter act in a coordinated... 

ABC Transporters. Table 1 Substrates of ABC-transporters involved in multidrug resistance (MDR)... 

B orst P, Elferink RO (2002) Mammalian ABC transporters in health and disease. Annu Rev Biochem 71 537-592... 

Currently, five different molecular classes of mdr efflux pumps are known [5], While pumps of the the ATP-binding cassette (ABC) transporter superfamily are driven by ATP hydrolysis, the other four superfamilies called resistance-nodulation-division (RND), major facilitator superfamily (MFS), multidrug and toxic compound extrusion (MATE), and small multidrag resistance transporter (SMR) are driven by the proton-motive force across the cytoplasmic membrane. Usually a single pump protein is located within the cytoplasmic membrane. However, the RND-type pumps which are restricted to Gram-negative bacteria consist of two additional components, a periplasmic membrane fusion protein (MFP) which connects the efflux pump to an outer... 

SURs are members of the ATP-binding cassette (ABC) family of proteins ( ABC transporters) with a typical ABC core consisting of two bundles of six... 

Bryan J, Munoz A, Zhang X et al (2007) ABCC8 and ABCC9 ABC transporters that regulate K+ channels. Pfliigers Arch 453 703-718... 

The breast cancer resistance protein (BCRP) belongs to the G-branch of the ABC-transporter family (ABCG2). In contrast to most other ABC-proteins, BCRP consists of only one transmembrane domain (TDM) with one nucleotide binding fold (NBF) at its C-terminus. Because of this structural characteristic BCRP as well as other ABC-transporters with only one TMD are termed half transporters. To achieve functional activity these transporters have to form hetero- or homodimers. BCRP is involved in the multidrug resistance of certain tumors and transports endogenous compounds like cholesterol and steroid hormones. 

The blood-brain barrier (BBB) forms a physiological barrier between the central nervous system and the blood circulation. It consists of glial cells and a special species of endothelial cells, which form tight junctions between each other thereby inhibiting paracellular transport. In addition, the endothelial cells of the BBB express a variety of ABC-transporters to protect the brain tissue against toxic metabolites and xenobiotics. The BBB is permeable to water, glucose, sodium chloride and non-ionised lipid-soluble molecules but large molecules such as peptides as well as many polar substances do not readily permeate the battier. 

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