Modeling kinetics of subcellular disposition of chemicals.
Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, North Dakota 58105, USA. firstname.lastname@example.orgShow MeSH
Mentions: The ABC transporters are integral membrane proteins that are folded into several trans-membrane domains (TMDs), each composed of fewer than 10, and most commonly 6 trans-membrane helices. They frequently contain extracellular N-glycosylation branches that do not seem to be associated with transport function.(1158) The minimal functional unit of an ABC transporter involved in the efflux of chemicals consists of two TMDs and two nucleotide binding domains (NBDs or ABCs),1159,1160 as illustrated in Figure 9. The TMDs contain one or more substrate binding sites. The TMDs exhibit some sequence similarity only if they mediate transport in the same direction.(1161) The NBD sequences are much more conserved than those of TMDs, because each contains the conserved Walker A and B motifs, which are shared by numerous ATP-binding proteins,(1162) and an ABC signature motif (ALSGGQ) that is also called the C motif. The bound nucleotides (Figure 9) are sandwiched between the C motif and the Walker A motif from the opposite NBD.1161,1163,1164 The NBDs act as molecular motors, initiating conformational changes of TMDs.(1160) The same motor seems to be connected to differing translocation channels. Therefore, a common mechanism may be shared by the majority of ABC transporters.(1161)
Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, North Dakota 58105, USA. email@example.com