The topography of transmembrane segment six is altered during the catalytic cycle of P-glycoprotein.
AuthorsRothnie A, Storm J, Campbell J, Linton KJ, Kerr ID, Callaghan R
JournalJ Biol Chem
PubMed ID15192095
'Structural evidence has demonstrated that P-glycoprotein (P-gp) undergoes considerable conformational changes during catalysis, and these alterations are important in drug interaction. Knowledge of which regions in P-gp undergo conformational alterations will provide vital information to elucidate the locations of drug binding sites and the mechanism of coupling. A number of ... More
Cytosolic region of TM6 in P-glycoprotein: topographical analysis and functional perturbation by site directed labeling.
'Reduced intracellular drug accumulation due to the activity of the drug efflux pump ABC (B1) is a major mechanism in the resistance of cancer cells to chemotherapy. ABC (B1) is a poly specific transporter, and the molecular mechanism of its complex translocation process remains to be elucidated. To understand the ... More
Cytotoxic targeting of F9 teratocarcinoma tumours with anti-ED-B fibronectin scFv antibody modified liposomes.
'We prepared small unilamellar liposomes derivatised with single chain antibody fragments specific for the ED-B domain of B-fibronectin. This extracellular matrix associated protein is expressed around newly forming blood vessels in the vicinity of many types of tumours. The single chain antibody fragments were functionalised by introduction of C-terminal cysteines ... More
Role of transmembrane domain 8 in substrate selectivity and translocation of SteT, a member of the L-amino acid transporter (LAT) family.
AuthorsBartoccioni P, Del Rio C, Ratera M, Kowalczyk L, Baldwin JM, Zorzano A, Quick M, Baldwin SA, Vázquez-Ibar JL, Palacín M,
JournalJ Biol Chem
PubMed ID20610400
System l-amino acid transporters (LAT) belong to the amino acid, polyamine, and organic cation superfamily of transporters and include the light subunits of heteromeric amino acid transporters and prokaryotic homologues. Cysteine reactivity of SteT (serine/threonine antiporter) has been used here to study the substrate-binding site of LAT transporters. Residue Cys-291, ... More