Matches in SemOpenAlex for { <https://semopenalex.org/work/W1518517610> ?p ?o ?g. }
Showing items 1 to 80 of
80
with 100 items per page.
- W1518517610 abstract "Cocaine is a highly addictive drug that targets the presynaptic dopamine transporter (DAT) and blocks the reuptake of dopamine resulting in heightened dopaminergic neurotransmission. The DAT is a 12 transmembrane (TM) spanning protein with residues from TMs 1, 3, 6, and 8 comprising the substrate and putative inhibitor binding sites; although recent studies indicate the presence of an inhibitor binding site in the external vestibule located above the substrate-binding site. Despite decades of research, the binding site of cocaine has yet to be fully characterized. To address this question, we are mapping the attachment sites of irreversible cocaine analogs, [125I]MFZ 2-24, [125I] RTI 82, and [125I]JHC 2-48, using insight gained from in silico docking with DAT comparative models. These compounds have a cocaine pharmacophore with analog specific azido group that adducts to the protein. To determine the adduction site of [125I]JHC 2-48 we are using methionine substitution mutagenesis to generate custom protease sites for cleavage by cyanogen bromide (CNBr). The fragments generated from the CNBr proteolysis of [125I]JHC 2-48 labeled DAT were visualized via SDS-PAGE and autoradiography. The preliminary results obtained thus far have determined the [125I]JHC 2-48 attachment site to be C-terminal to TM7. Peptide map analyses of other cocaine analogs, [125I]MFZ 2-24 and [125I] RTI 82, have determined [125I]MFZ 2-24 adducts to TM1 and [125I]RTI 82 adducts to TM6. Taken together, our data strongly indicate cocaine binds near the substrate binding site. Grant Funding Source: Supported by: DA027845 and NIDA-IRP" @default.
- W1518517610 created "2016-06-24" @default.
- W1518517610 creator A5005536421 @default.
- W1518517610 creator A5010869299 @default.
- W1518517610 creator A5011553712 @default.
- W1518517610 creator A5012510426 @default.
- W1518517610 creator A5018939644 @default.
- W1518517610 creator A5030150313 @default.
- W1518517610 creator A5037113655 @default.
- W1518517610 creator A5051751193 @default.
- W1518517610 creator A5061926206 @default.
- W1518517610 creator A5081734448 @default.
- W1518517610 creator A5089602272 @default.
- W1518517610 date "2014-04-01" @default.
- W1518517610 modified "2023-09-29" @default.
- W1518517610 title "Identification of the attachment site for the cocaine analog [ 125 I]JHC 2‐48 on the dopamine transporter (803.7)" @default.
- W1518517610 doi "https://doi.org/10.1096/fasebj.28.1_supplement.803.7" @default.
- W1518517610 hasPublicationYear "2014" @default.
- W1518517610 type Work @default.
- W1518517610 sameAs 1518517610 @default.
- W1518517610 citedByCount "0" @default.
- W1518517610 crossrefType "journal-article" @default.
- W1518517610 hasAuthorship W1518517610A5005536421 @default.
- W1518517610 hasAuthorship W1518517610A5010869299 @default.
- W1518517610 hasAuthorship W1518517610A5011553712 @default.
- W1518517610 hasAuthorship W1518517610A5012510426 @default.
- W1518517610 hasAuthorship W1518517610A5018939644 @default.
- W1518517610 hasAuthorship W1518517610A5030150313 @default.
- W1518517610 hasAuthorship W1518517610A5037113655 @default.
- W1518517610 hasAuthorship W1518517610A5051751193 @default.
- W1518517610 hasAuthorship W1518517610A5061926206 @default.
- W1518517610 hasAuthorship W1518517610A5081734448 @default.
- W1518517610 hasAuthorship W1518517610A5089602272 @default.
- W1518517610 hasConcept C104317684 @default.
- W1518517610 hasConcept C107824862 @default.
- W1518517610 hasConcept C116569031 @default.
- W1518517610 hasConcept C118892022 @default.
- W1518517610 hasConcept C149011108 @default.
- W1518517610 hasConcept C169760540 @default.
- W1518517610 hasConcept C170493617 @default.
- W1518517610 hasConcept C185592680 @default.
- W1518517610 hasConcept C2776755682 @default.
- W1518517610 hasConcept C2909816965 @default.
- W1518517610 hasConcept C513476851 @default.
- W1518517610 hasConcept C55493867 @default.
- W1518517610 hasConcept C86803240 @default.
- W1518517610 hasConcept C96267730 @default.
- W1518517610 hasConceptScore W1518517610C104317684 @default.
- W1518517610 hasConceptScore W1518517610C107824862 @default.
- W1518517610 hasConceptScore W1518517610C116569031 @default.
- W1518517610 hasConceptScore W1518517610C118892022 @default.
- W1518517610 hasConceptScore W1518517610C149011108 @default.
- W1518517610 hasConceptScore W1518517610C169760540 @default.
- W1518517610 hasConceptScore W1518517610C170493617 @default.
- W1518517610 hasConceptScore W1518517610C185592680 @default.
- W1518517610 hasConceptScore W1518517610C2776755682 @default.
- W1518517610 hasConceptScore W1518517610C2909816965 @default.
- W1518517610 hasConceptScore W1518517610C513476851 @default.
- W1518517610 hasConceptScore W1518517610C55493867 @default.
- W1518517610 hasConceptScore W1518517610C86803240 @default.
- W1518517610 hasConceptScore W1518517610C96267730 @default.
- W1518517610 hasIssue "S1" @default.
- W1518517610 hasLocation W15185176101 @default.
- W1518517610 hasOpenAccess W1518517610 @default.
- W1518517610 hasPrimaryLocation W15185176101 @default.
- W1518517610 hasRelatedWork W1984704777 @default.
- W1518517610 hasRelatedWork W1991437467 @default.
- W1518517610 hasRelatedWork W1999737174 @default.
- W1518517610 hasRelatedWork W2019647316 @default.
- W1518517610 hasRelatedWork W2044609389 @default.
- W1518517610 hasRelatedWork W2052590859 @default.
- W1518517610 hasRelatedWork W2100268743 @default.
- W1518517610 hasRelatedWork W2119117083 @default.
- W1518517610 hasRelatedWork W4237144016 @default.
- W1518517610 hasRelatedWork W2123090520 @default.
- W1518517610 hasVolume "28" @default.
- W1518517610 isParatext "false" @default.
- W1518517610 isRetracted "false" @default.
- W1518517610 magId "1518517610" @default.
- W1518517610 workType "article" @default.