8cc7: Difference between revisions

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New page: '''Unreleased structure''' The entry 8cc7 is ON HOLD Authors: Description: Category: Unreleased Structures
 
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'''Unreleased structure'''


The entry 8cc7 is ON HOLD
==Mouse serotonin 5-HT3A receptor in complex with PZ-1939==
<StructureSection load='8cc7' size='340' side='right'caption='[[8cc7]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8cc7]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CC7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CC7 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=U9Q:1-(3-chlorophenyl)sulfonyl-4-piperazin-1-yl-pyrrolo[3,2-c]quinoline'>U9Q</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8cc7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cc7 OCA], [https://pdbe.org/8cc7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cc7 RCSB], [https://www.ebi.ac.uk/pdbsum/8cc7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cc7 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/5HT3A_MOUSE 5HT3A_MOUSE] This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The multifactorial origin and neurochemistry of Alzheimer's disease (AD) call for the development of multitarget treatment strategies. We report a first-in-class triple acting compound that targets serotonin type 6 and 3 receptors (5-HT-Rs) and monoamine oxidase type B (MAO-B) as an approach for treating AD. The key structural features required for MAO-B inhibition and 5-HT(6)R antagonism and interaction with 5-HT(3)R were determined using molecular dynamic simulations and cryo-electron microscopy, respectively. Bioavailable PZ-1922 reversed scopolamine-induced cognitive deficits in the novel object recognition test. Furthermore, it displayed superior pro-cognitive properties compared to intepirdine (a 5-HT(6)R antagonist) in the AD model, which involved intracerebroventricular injection of an oligomeric solution of amyloid-beta peptide (oAbeta) in the T-maze test in rats. PZ-1922, but not intepirdine, restored levels of biomarkers characteristic of the debilitating effects of oAbeta. These data support the potential of a multitarget approach involving the joint modulation of 5-HT(6)R/5-HT(3)R/MAO-B in AD.


Authors:  
Superiority of the Triple-Acting 5-HT(6)R/5-HT(3)R Antagonist and MAO-B Reversible Inhibitor PZ-1922 over 5-HT(6)R Antagonist Intepirdine in Alleviation of Cognitive Deficits in Rats.,Grychowska K, Lopez-Sanchez U, Vitalis M, Canet G, Satala G, Olejarz-Maciej A, Golebiowska J, Kurczab R, Pietrus W, Kubacka M, Moreau C, Walczak M, Blicharz-Futera K, Bento O, Bantreil X, Subra G, Bojarski AJ, Lamaty F, Becamel C, Zussy C, Chaumont-Dubel S, Popik P, Nury H, Marin P, Givalois L, Zajdel P J Med Chem. 2023 Nov 9;66(21):14928-14947. doi: 10.1021/acs.jmedchem.3c01482. , Epub 2023 Oct 5. PMID:37797083<ref>PMID:37797083</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 8cc7" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Lopez-Sanchez U]]
[[Category: Nury H]]

Latest revision as of 12:31, 17 October 2024

Mouse serotonin 5-HT3A receptor in complex with PZ-1939Mouse serotonin 5-HT3A receptor in complex with PZ-1939

Structural highlights

8cc7 is a 5 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

5HT3A_MOUSE This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel.

Publication Abstract from PubMed

The multifactorial origin and neurochemistry of Alzheimer's disease (AD) call for the development of multitarget treatment strategies. We report a first-in-class triple acting compound that targets serotonin type 6 and 3 receptors (5-HT-Rs) and monoamine oxidase type B (MAO-B) as an approach for treating AD. The key structural features required for MAO-B inhibition and 5-HT(6)R antagonism and interaction with 5-HT(3)R were determined using molecular dynamic simulations and cryo-electron microscopy, respectively. Bioavailable PZ-1922 reversed scopolamine-induced cognitive deficits in the novel object recognition test. Furthermore, it displayed superior pro-cognitive properties compared to intepirdine (a 5-HT(6)R antagonist) in the AD model, which involved intracerebroventricular injection of an oligomeric solution of amyloid-beta peptide (oAbeta) in the T-maze test in rats. PZ-1922, but not intepirdine, restored levels of biomarkers characteristic of the debilitating effects of oAbeta. These data support the potential of a multitarget approach involving the joint modulation of 5-HT(6)R/5-HT(3)R/MAO-B in AD.

Superiority of the Triple-Acting 5-HT(6)R/5-HT(3)R Antagonist and MAO-B Reversible Inhibitor PZ-1922 over 5-HT(6)R Antagonist Intepirdine in Alleviation of Cognitive Deficits in Rats.,Grychowska K, Lopez-Sanchez U, Vitalis M, Canet G, Satala G, Olejarz-Maciej A, Golebiowska J, Kurczab R, Pietrus W, Kubacka M, Moreau C, Walczak M, Blicharz-Futera K, Bento O, Bantreil X, Subra G, Bojarski AJ, Lamaty F, Becamel C, Zussy C, Chaumont-Dubel S, Popik P, Nury H, Marin P, Givalois L, Zajdel P J Med Chem. 2023 Nov 9;66(21):14928-14947. doi: 10.1021/acs.jmedchem.3c01482. , Epub 2023 Oct 5. PMID:37797083[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Grychowska K, López-Sánchez U, Vitalis M, Canet G, Satała G, Olejarz-Maciej A, Gołębiowska J, Kurczab R, Pietruś W, Kubacka M, Moreau C, Walczak M, Blicharz-Futera K, Bento O, Bantreil X, Subra G, Bojarski AJ, Lamaty F, Becamel C, Zussy C, Chaumont-Dubel S, Popik P, Nury H, Marin P, Givalois L, Zajdel P. Superiority of the Triple-Acting 5-HT(6)R/5-HT(3)R Antagonist and MAO-B Reversible Inhibitor PZ-1922 over 5-HT(6)R Antagonist Intepirdine in Alleviation of Cognitive Deficits in Rats. J Med Chem. 2023 Nov 9;66(21):14928-14947. PMID:37797083 doi:10.1021/acs.jmedchem.3c01482

8cc7, resolution 3.00Å

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