2qju

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[[Image:2qju.jpg|left|200px]]
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{{Seed}}
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{{STRUCTURE_2qju| PDB=2qju | SCENE= }}
{{STRUCTURE_2qju| PDB=2qju | SCENE= }}
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'''Crystal Structure of an NSS Homolog with Bound Antidepressant'''
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===Crystal Structure of an NSS Homolog with Bound Antidepressant===
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==Overview==
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Tricyclic antidepressants exert their pharmacological effect-inhibiting the reuptake of serotonin, norepinephrine, and dopamine-by directly blocking neurotransmitter transporters (SERT, NET, and DAT, respectively) in the presynaptic membrane. The drug-binding site and the mechanism of this inhibition are poorly understood. We determined the crystal structure at 2.9 angstroms of the bacterial leucine transporter (LeuT), a homolog of SERT, NET, and DAT, in complex with leucine and the antidepressant desipramine. Desipramine binds at the inner end of the extracellular cavity of the transporter and is held in place by a hairpin loop and by a salt bridge. This binding site is separated from the leucine-binding site by the extracellular gate of the transporter. By directly locking the gate, desipramine prevents conformational changes and blocks substrate transport. Mutagenesis experiments on human SERT and DAT indicate that both the desipramine-binding site and its inhibition mechanism are probably conserved in the human neurotransmitter transporters.
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(as it appears on PubMed at http://www.pubmed.gov), where 17690258 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17690258}}
==About this Structure==
==About this Structure==
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[[Category: Transmembrane transport]]
[[Category: Transmembrane transport]]
[[Category: Transport protein]]
[[Category: Transport protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 15:04:48 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 19:35:41 2008''

Revision as of 16:35, 28 July 2008

Image:2qju.png

Template:STRUCTURE 2qju

Crystal Structure of an NSS Homolog with Bound Antidepressant

Template:ABSTRACT PUBMED 17690258

About this Structure

2QJU is a Single protein structure of sequence from Aquifex aeolicus. Full crystallographic information is available from OCA.

Reference

LeuT-desipramine structure reveals how antidepressants block neurotransmitter reuptake., Zhou Z, Zhen J, Karpowich NK, Goetz RM, Law CJ, Reith ME, Wang DN, Science. 2007 Sep 7;317(5843):1390-3. Epub 2007 Aug 9. PMID:17690258

Page seeded by OCA on Mon Jul 28 19:35:41 2008

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