Anthony M. George's ABC Transporters - 40 Years on PDF

By Anthony M. George

ISBN-10: 3319234757

ISBN-13: 9783319234755

ISBN-10: 3319234765

ISBN-13: 9783319234762

This ebook presents new structural, biochemical, and medical info on ABC transporters. The authors discover and describe the cutting-edge of study, wisdom, and customers for the longer term for this significant family members of proteins. the 1st ABC transporter used to be chanced on in 1973 and was once named P-glycoprotein. It elicits resistance to cytotoxic medications, mainly in human tumours, during which chemotherapy failure is saw in approximately 50% of instances. including its complicated pharmacology, or even a suspected function in Alzheimer’s illness, this ABC transporter nonetheless eludes a medical method to its multidrug resistance estate. ABC transporters are critical membrane energetic proteins they usually belong to at least one of the most important protein households throughout all species. Their myriad roles surround the import or export of a various variety of allocrites, together with ion, meals, peptides, polysaccharides, lipids, and xenobiotics. they're of significant clinical significance with many individuals elaborating multidrug resistance in micro organism, fungi, yeast, parasites, and people. different ABC transporters are interested in a couple of inherited illnesses, together with cystic fibrosis, macular degeneration, gout, and a number of other metabolic disorders

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Additional info for ABC Transporters - 40 Years on

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Phylogenetic analyses indicate that these duplications occurred independently, while a tandem gene duplication occurred in the case of the TAP family (Hughes 1994; Dean and Allikmets 1995). ABCB1 is closely related to the hemolysin A-secreting HlyB transporter (Holland et al. 1991) and lipid A transporter MsbA (Karow and Georgopoulos 1993) in Gram-negative bacteria and multidrug transporter LmrA and orthologs in Gram-positive bacteria (van Veen et al. 1996; van Veen and Konings 1997). In accordance with the endosymbiont theory, one hypothesis to explain this observation is that eukaryotic ABCB1 and TAP genes are descended from a mitochondrial gene or genes that were subsequently translocated to the nuclear genome.

In both cases, the NBD subunits have a C-terminal regulatory domain albeit with distinct folds (Gerber et al. 2008; Johnson et al. 2012). The MetN2I2 system is inhibited when cytoplasmic levels of methionine reach threshold values (Kadner 1977), and the binding of methionine to the C-terminal domain stabilizes the transporter in the inward-facing conformation, similar to what IIAglc does to the maltose transporter. The ModB2C2 system is inhibited by the binding of molybdate or tungstate to its C-terminal regulatory domain.

This is in agreement with EPR studies performed on ThiT, which showed that the major difference between substrate-bound and substrate-free ThiT is a conformational change of the L1 loop (Majsnerowska et al. 2013). In the structure of the complete transporters, the S-component adopts a highly unusual orientation, lying almost parallel in the membrane like it has toppled over from the orientation of the solitary S-components (SI in Fig. 9) (Wang et al. 2013; Xu et al. 2013; Zhang et al. 2014). The S-component interacts with EcfT, but not with the NBDs, via two interaction sites with the interactions between TM1, TM2, and the C-terminal end of TM6 of the S-components and the coupling helices of EcfT forming the largest interaction interface.

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ABC Transporters - 40 Years on by Anthony M. George

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