{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/18548"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/18548","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"STRUCTURE-FUNCTION ANALYSIS OF THE HUMAN EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 1","abstract":"Site-directed mutagenesis was used to target residues within transmembrane domains 1 and 2 of the human equilibrative nucleoside transporter 1 (hENTl), in order to assess their contributions to transporter functionality. Through affinity changes in [ H]NBMPR binding, competitive inhibition profiles with ENT1 inhibitors and [ H]2- chloroadenosine uptake, these residues were found to make minor, but statistically significant, contributions to the inhibitor and/or substrate binding site of hENTl. An initial study was also undertaken to probe the potential oligomerization of hENTl. Typically considered to be a monomer to this date, under the native conditions of Blue Native Electrophoresis, hENTl was found to possess a molecular mass of 160 kDa. This is approximately three times the size of the known 55kDa hENTl monomer. Targeted site-directed mutagenesis of GxxxG motifs within the transporter, known to play a role in oligomerization, did not appear to affect the higher molecular mass hENTl complex observed","abstract_html":"Site-directed mutagenesis was used to target residues within transmembrane domains 1 and 2 of the human equilibrative nucleoside transporter 1 (hENTl), in order to assess their contributions to transporter functionality. Through affinity changes in [ H]NBMPR binding, competitive inhibition profiles with ENT1 inhibitors and [ H]2- chloroadenosine uptake, these residues were found to make minor, but statistically significant, contributions to the inhibitor and/or substrate binding site of hENTl. An initial study was also undertaken to probe the potential oligomerization of hENTl. Typically considered to be a monomer to this date, under the native conditions of Blue Native Electrophoresis, hENTl was found to possess a molecular mass of 160 kDa. This is approximately three times the size of the known 55kDa hENTl monomer. Targeted site-directed mutagenesis of GxxxG motifs within the transporter, known to play a role in oligomerization, did not appear to affect the higher molecular mass hENTl complex observed","abstract_has_math":false,"creators":["Cunningham, Frances Kay Marie"],"institution":null,"degree_name":"M Sc","degree_level":null,"degree_discipline":"Pharmacology and Toxicology","degree_department":null,"school":null,"contributors":[],"advisors":["Hammond, James R."],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-01-01","date_published":"2011-01-01","updated_at":"2026-07-27T21:55:59Z","subjects":["equilibrative nucleoside transporters","site-directed mutagenesis","transmembrane domains 1 and 2","oligomerization","blue native electrophoresis","GxxxG motif"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/18548","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Hammond, James R."]},{"key":"dc:creator","label":"Author","values":["Cunningham, Frances Kay Marie"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-06-25T18:51:22Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-06-25T18:51:22Z"]},{"key":"dc:date.issued","label":"Date","values":["2011-01-01"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Pharmacology and Toxicology"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M Sc"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["equilibrative nucleoside transporters","site-directed mutagenesis","transmembrane domains 1 and 2","oligomerization","blue native electrophoresis","GxxxG motif"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/18548"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Site-directed mutagenesis was used to target residues within transmembrane domains 1 and 2 of the human equilibrative nucleoside transporter 1 (hENTl), in order to assess their contributions to transporter functionality. Through affinity changes in [ H]NBMPR binding, competitive inhibition profiles with ENT1 inhibitors and [ H]2- chloroadenosine uptake, these residues were found to make minor, but statistically significant, contributions to the inhibitor and/or substrate binding site of hENTl. An initial study was also undertaken to probe the potential oligomerization of hENTl. Typically considered to be a monomer to this date, under the native conditions of Blue Native Electrophoresis, hENTl was found to possess a molecular mass of 160 kDa. This is approximately three times the size of the known 55kDa hENTl monomer. Targeted site-directed mutagenesis of GxxxG motifs within the transporter, known to play a role in oligomerization, did not appear to affect the higher molecular mass hENTl complex observed"]},{"key":"dc:title","label":"Title","values":["STRUCTURE-FUNCTION ANALYSIS OF THE HUMAN EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 1"]}]}],"canonical_facts":{"dc:contributor.advisor":["Hammond, James R."],"dc:creator":["Cunningham, Frances Kay Marie"],"dc:date.accessioned":["2025-06-25T18:51:22Z"],"dc:date.available":["2025-06-25T18:51:22Z"],"dc:date.issued":["2011-01-01"],"dc:description.abstract":["Site-directed mutagenesis was used to target residues within transmembrane domains 1 and 2 of the human equilibrative nucleoside transporter 1 (hENTl), in order to assess their contributions to transporter functionality. Through affinity changes in [ H]NBMPR binding, competitive inhibition profiles with ENT1 inhibitors and [ H]2- chloroadenosine uptake, these residues were found to make minor, but statistically significant, contributions to the inhibitor and/or substrate binding site of hENTl. An initial study was also undertaken to probe the potential oligomerization of hENTl. Typically considered to be a monomer to this date, under the native conditions of Blue Native Electrophoresis, hENTl was found to possess a molecular mass of 160 kDa. This is approximately three times the size of the known 55kDa hENTl monomer. Targeted site-directed mutagenesis of GxxxG motifs within the transporter, known to play a role in oligomerization, did not appear to affect the higher molecular mass hENTl complex observed"],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/18548"],"dc:subject":["equilibrative nucleoside transporters","site-directed mutagenesis","transmembrane domains 1 and 2","oligomerization","blue native electrophoresis","GxxxG motif"],"dc:title":["STRUCTURE-FUNCTION ANALYSIS OF THE HUMAN EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 1"],"dc:type":["thesis"],"thesis:degree_discipline":["Pharmacology and Toxicology"],"thesis:degree_name":["M Sc"]},"updated_at":"2026-07-27T21:55:59Z"}