caa a22 4500 463208323 CHVBK 20180405153132.0 cr unu---uuuuu 170326e20071201xx s 000 0 eng 10.1007/s10863-007-9115-9 doi (NATIONALLICENCE)springer-10.1007/s10863-007-9115-9 Genomics and the mechanism of P-glycoprotein (ABCB1) [Elektronische Daten] [Zuben Sauna, In-Wha Kim, Suresh Ambudkar] The development of effective clinical interventions against multidrug resistance (MDR) in cancer remains a significant challenge. Single nucleotide polymorphisms (SNPs) contribute to wide variations in how individuals respond to medications and there are several SNPs in human P-glycoprotein (P-gp) that may influence the interactions of drug-substrates with the transporter. Interestingly, even some of the synonymous SNPs have functional consequences for P-gp. It is also becoming increasingly evident that an understanding of the transport pathway of P-gp may be necessary to design effective modulators. In this review we discuss: (1) The potential importance of SNPs (both synonymous and non-synonymous) in MDR and (2) How new concepts that have emerged from structural studies with isolated nucleotide binding domains of bacterial ABC transporters have prompted biochemical studies on P-gp, leading to a better understanding of the mechanism of P-gp mediated transport. Our results suggest that the power-stroke is provided only after formation of the pre-hydrolysis transition-like (E·S) state during ATP hydrolysis. Springer Science+Business Media, LLC, 2007 ATP-binding cassette nationallicence P-glycoprotein nationallicence Multidrug resistance nationallicence ATP hydrolysis nationallicence Catalytic/transport pathway nationallicence Single nucleotide polymorphism nationallicence Sauna Zuben Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Building 37, Room 2120, 37 Convent Drive, 20892-4256, Bethesda, MD, USA aut Kim In-Wha Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Building 37, Room 2120, 37 Convent Drive, 20892-4256, Bethesda, MD, USA aut Ambudkar Suresh Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Building 37, Room 2120, 37 Convent Drive, 20892-4256, Bethesda, MD, USA aut Journal of Bioenergetics and Biomembranes Springer US; http://www.springer-ny.com 39/5-6(2007-12-01), 481-487 0145-479X 39:5-6<481 2007 39 10863 https://doi.org/10.1007/s10863-007-9115-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10863-007-9115-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sauna Zuben Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Building 37, Room 2120, 37 Convent Drive, 20892-4256, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Kim In-Wha Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Building 37, Room 2120, 37 Convent Drive, 20892-4256, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Ambudkar Suresh Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Building 37, Room 2120, 37 Convent Drive, 20892-4256, Bethesda, MD, USA aut NATIONALLICENCE 773 0- Journal of Bioenergetics and Biomembranes Springer US; http://www.springer-ny.com 39/5-6(2007-12-01), 481-487 0145-479X 39:5-6<481 2007 39 10863 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer