5fyx: Difference between revisions

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New page: '''Unreleased structure''' The entry 5fyx is ON HOLD until Paper Publication Authors: Martinez-Gonzalez, L., Chaves-Sanjuan, A., Infantes, L., Sanchez-Barrena, M.J. Description: Crysta...
 
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'''Unreleased structure'''


The entry 5fyx is ON HOLD  until Paper Publication
==Crystal structure of Drosophila NCS-1 bound to penothiazine FD16==
<StructureSection load='5fyx' size='340' side='right'caption='[[5fyx]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5fyx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FYX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FYX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FD6:N-[2-(2-CHLORANYLPHENOTHIAZIN-10-YL)ETHYL]-4-METHYL-PIPERAZIN-1-AMINE'>FD6</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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=5fyx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fyx OCA], [https://pdbe.org/5fyx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fyx RCSB], [https://www.ebi.ac.uk/pdbsum/5fyx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fyx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9VWX8_DROME Q9VWX8_DROME]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The protein complex formed by the Ca2+ sensor neuronal calcium sensor 1 (NCS-1) and the guanine exchange factor protein Ric8a coregulates synapse number and probability of neurotransmitter release, emerging as a potential therapeutic target for diseases affecting synapses, such as fragile X syndrome (FXS), the most common heritable autism disorder. Using crystallographic data and the virtual screening of a chemical library, we identified a set of heterocyclic small molecules as potential inhibitors of the NCS-1/Ric8a interaction. The aminophenothiazine FD44 interferes with NCS-1/Ric8a binding, and it restores normal synapse number and associative learning in a Drosophila FXS model. The synaptic effects elicited by FD44 feeding are consistent with the genetic manipulation of NCS-1. The crystal structure of NCS-1 bound to FD44 and the structure-function studies performed with structurally close analogs explain the FD44 specificity and the mechanism of inhibition, in which the small molecule stabilizes a mobile C-terminal helix inside a hydrophobic crevice of NCS-1 to impede Ric8a interaction. Our study shows the drugability of the NCS-1/Ric8a interface and uncovers a suitable region in NCS-1 for development of additional drugs of potential use on FXS and related synaptic disorders.


Authors: Martinez-Gonzalez, L., Chaves-Sanjuan, A., Infantes, L., Sanchez-Barrena, M.J.
Interference of the complex between NCS-1 and Ric8a with phenothiazines regulates synaptic function and is an approach for fragile X syndrome.,Mansilla A, Chaves-Sanjuan A, Campillo NE, Semelidou O, Martinez-Gonzalez L, Infantes L, Gonzalez-Rubio JM, Gil C, Conde S, Skoulakis EM, Ferrus A, Martinez A, Sanchez-Barrena MJ Proc Natl Acad Sci U S A. 2017 Feb 7;114(6):E999-E1008. doi:, 10.1073/pnas.1611089114. Epub 2017 Jan 24. PMID:28119500<ref>PMID:28119500</ref>


Description: Crystal structure of Frq bound to a ligand
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Sanchez-Barrena, M.J]]
<div class="pdbe-citations 5fyx" style="background-color:#fffaf0;"></div>
[[Category: Chaves-Sanjuan, A]]
== References ==
[[Category: Infantes, L]]
<references/>
[[Category: Martinez-Gonzalez, L]]
__TOC__
</StructureSection>
[[Category: Drosophila melanogaster]]
[[Category: Large Structures]]
[[Category: Chaves-Sanjuan A]]
[[Category: Infantes L]]
[[Category: Martinez-Gonzalez L]]
[[Category: Sanchez-Barrena MJ]]
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