Human dopamine transporter: the first implementation of a combined in silico/in vitro approach revealing the substrate and inhibitor specificities
Parkinson’s disease (PD) is characterized by the loss of dopamine-generating neurons in the substantia nigra and corpus striatum. Current treatments alleviate PD symptoms rather than exerting neuroprotective effect on dopaminergic neurons. New drugs targeting the dopaminergic neurons by specific upt...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
2019
|
| In: |
Journal of biomolecular structure & dynamics
Year: 2018, Volume: 37, Issue: 2, Pages: 291-306 |
| ISSN: | 1538-0254 |
| DOI: | 10.1080/07391102.2018.1426044 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1080/07391102.2018.1426044
|
| Author Notes: | Teodora Djikic, Yasmina Martí, Francesca Spyrakis, Thorsten Lau, Paolo Benedetti, Gavin Davey, Patrick Schloss & Kemal Yelekci |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1667826891 | ||
| 003 | DE-627 | ||
| 005 | 20230427035411.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 190624r20192018xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/07391102.2018.1426044 |2 doi | |
| 035 | |a (DE-627)1667826891 | ||
| 035 | |a (DE-599)KXP1667826891 | ||
| 035 | |a (OCoLC)1341229279 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Djikic, Teodora |e VerfasserIn |0 (DE-588)1189092085 |0 (DE-627)166782709X |4 aut | |
| 245 | 1 | 0 | |a Human dopamine transporter |b the first implementation of a combined in silico/in vitro approach revealing the substrate and inhibitor specificities |c Teodora Djikic, Yasmina Martí, Francesca Spyrakis, Thorsten Lau, Paolo Benedetti, Gavin Davey, Patrick Schloss & Kemal Yelekci |
| 264 | 1 | |c 2019 | |
| 300 | |a 16 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Published online: 26 Jan 2018 | ||
| 500 | |a Gesehen am 24.06.2019 | ||
| 520 | |a Parkinson’s disease (PD) is characterized by the loss of dopamine-generating neurons in the substantia nigra and corpus striatum. Current treatments alleviate PD symptoms rather than exerting neuroprotective effect on dopaminergic neurons. New drugs targeting the dopaminergic neurons by specific uptake through the human dopamine transporter (hDAT) could represent a viable strategy for establishing selective neuroprotection. Molecules able to increase the bioactive amount of extracellular dopamine, thereby enhancing and compensating a loss of dopaminergic neurotransmission, and to exert neuroprotective response because of their accumulation in the cytoplasm, are required. By means of homology modeling, molecular docking, and molecular dynamics simulations, we have generated 3D structure models of hDAT in complex with substrate and inhibitors. Our results clearly reveal differences in binding affinity of these compounds to the hDAT in the open and closed conformations, critical for future drug design. The established in silico approach allowed the identification of promising substrate compounds that were subsequently analyzed for their efficiency in inhibiting hDAT-dependent fluorescent substrate uptake, through in vitro live cell imaging experiments. Taken together, our work presents the first implementation of a combined in silico/in vitro approach enabling the selection of promising dopaminergic neuron-specific substrates. | ||
| 534 | |c 2018 | ||
| 650 | 4 | |a DAT | |
| 650 | 4 | |a molecular modeling | |
| 650 | 4 | |a neuroprotection | |
| 650 | 4 | |a substrates | |
| 650 | 4 | |a virtual screening | |
| 700 | 1 | |a Martí, Yasmina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Spyrakis, Francesca |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lau, Thorsten |e VerfasserIn |0 (DE-588)1141706628 |0 (DE-627)1000693643 |0 (DE-576)494472766 |4 aut | |
| 700 | 1 | |a Benedetti, Paolo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Davey, Gavin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schloss, Patrick |d 1955- |e VerfasserIn |0 (DE-588)1055972692 |0 (DE-627)792998227 |0 (DE-576)411983970 |4 aut | |
| 700 | 1 | |a Yelekci, Kemal |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of biomolecular structure & dynamics |d Abingdon [u.a.] : Taylor & Francis, 1983 |g 37(2019), 2, Seite 291-306 |h Online-Ressource |w (DE-627)352827769 |w (DE-600)2085732-9 |w (DE-576)367392798 |x 1538-0254 |7 nnas |a Human dopamine transporter the first implementation of a combined in silico/in vitro approach revealing the substrate and inhibitor specificities |
| 773 | 1 | 8 | |g volume:37 |g year:2019 |g number:2 |g pages:291-306 |g extent:16 |a Human dopamine transporter the first implementation of a combined in silico/in vitro approach revealing the substrate and inhibitor specificities |
| 856 | 4 | 0 | |u https://doi.org/10.1080/07391102.2018.1426044 |x Verlag |x Resolving-System |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20190624 | ||
| 993 | |a Article | ||
| 994 | |a 2019 | ||
| 998 | |g 1055972692 |a Schloss, Patrick |m 1055972692:Schloss, Patrick |d 60000 |e 60000PS1055972692 |k 0/60000/ |p 7 | ||
| 998 | |g 1141706628 |a Lau, Thorsten |m 1141706628:Lau, Thorsten |d 60000 |e 60000PL1141706628 |k 0/60000/ |p 4 | ||
| 999 | |a KXP-PPN1667826891 |e 348943580X | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"language":["eng"],"physDesc":[{"extent":"16 S."}],"relHost":[{"type":{"bibl":"periodical","media":"Online-Ressource"},"part":{"year":"2019","pages":"291-306","issue":"2","volume":"37","extent":"16","text":"37(2019), 2, Seite 291-306"},"titleAlt":[{"title":"JBSD"}],"title":[{"title_sort":"Journal of biomolecular structure & dynamics","title":"Journal of biomolecular structure & dynamics","subtitle":"JBSD"}],"id":{"issn":["1538-0254"],"eki":["352827769"],"zdb":["2085732-9"]},"recId":"352827769","pubHistory":["1.1983/84 -"],"note":["Gesehen am 18.01.2013"],"physDesc":[{"extent":"Online-Ressource"}],"disp":"Human dopamine transporter the first implementation of a combined in silico/in vitro approach revealing the substrate and inhibitor specificitiesJournal of biomolecular structure & dynamics","language":["eng"],"origin":[{"dateIssuedKey":"1983","dateIssuedDisp":"1983-","publisherPlace":"Abingdon [u.a.] ; Guilderland, NY","publisher":"Taylor & Francis ; Adenine Press"}]}],"note":["Published online: 26 Jan 2018","Gesehen am 24.06.2019"],"origin":[{"dateIssuedKey":"2019","dateIssuedDisp":"2019"}],"title":[{"title":"Human dopamine transporter","subtitle":"the first implementation of a combined in silico/in vitro approach revealing the substrate and inhibitor specificities","title_sort":"Human dopamine transporter"}],"person":[{"role":"aut","given":"Teodora","roleDisplay":"VerfasserIn","display":"Djikic, Teodora","family":"Djikic"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Martí, Yasmina","given":"Yasmina","family":"Martí"},{"role":"aut","family":"Spyrakis","roleDisplay":"VerfasserIn","given":"Francesca","display":"Spyrakis, Francesca"},{"role":"aut","family":"Lau","roleDisplay":"VerfasserIn","given":"Thorsten","display":"Lau, Thorsten"},{"role":"aut","family":"Benedetti","roleDisplay":"VerfasserIn","given":"Paolo","display":"Benedetti, Paolo"},{"role":"aut","family":"Davey","given":"Gavin","roleDisplay":"VerfasserIn","display":"Davey, Gavin"},{"roleDisplay":"VerfasserIn","given":"Patrick","display":"Schloss, Patrick","family":"Schloss","role":"aut"},{"family":"Yelekci","roleDisplay":"VerfasserIn","display":"Yelekci, Kemal","given":"Kemal","role":"aut"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"name":{"displayForm":["Teodora Djikic, Yasmina Martí, Francesca Spyrakis, Thorsten Lau, Paolo Benedetti, Gavin Davey, Patrick Schloss & Kemal Yelekci"]},"recId":"1667826891","id":{"eki":["1667826891"],"doi":["10.1080/07391102.2018.1426044"]}} | ||
| SRT | |a DJIKICTEODHUMANDOPAM2019 | ||