6qi4
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==NCS-1 bound to a ligand== | |
| + | <StructureSection load='6qi4' size='340' side='right'caption='[[6qi4]], [[Resolution|resolution]] 1.78Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6qi4]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QI4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QI4 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=FKW:2-(1~{H}-indol-3-yl)-~{N}-[(~{E})-(4-nitro-3-oxidanyl-phenyl)methylideneamino]ethanamide'>FKW</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6qi4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qi4 OCA], [http://pdbe.org/6qi4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qi4 RCSB], [http://www.ebi.ac.uk/pdbsum/6qi4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qi4 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/NCS1_HUMAN NCS1_HUMAN]] Neuronal calcium sensor, regulator of G protein-coupled receptor phosphorylation in a calcium dependent manner. Directly regulates GRK1 (RHOK), but not GRK2 to GRK5. Can substitute for calmodulin (By similarity). Stimulates PI4KB kinase activity (By similarity). Involved in long-term synaptic plasticity through its interaction with PICK1 (By similarity). May also play a role in neuron differentiation through inhibition of the activity of N-type voltage-gated calcium channel (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Dynamic combinatorial chemistry (DCC) has proven its potential in drug discovery speeding the identification of modulators of biological targets. However, the exchange chemistries typically take place under specific reaction conditions, with limited tools capable of operating under physiological parameters. Here we report a catalyzed protein-directed DCC working at low temperatures that allows the calcium sensor NCS-1 to find the best ligands in situ. Ultrafast NMR identifies the reaction intermediates of the acylhydrazone exchange, tracing the molecular assemblies and getting a real-time insight into the essence of DCC processes at physiological pH. Additionally, NMR, X-ray crystallography and computational methods are employed to elucidate structural and mechanistic aspects of the molecular recognition event. The DCC approach leads us to the identification of a compound stabilizing the NCS-1/Ric8a complex and whose therapeutic potential is proven in a Drosophila model of disease with synaptic alterations. | ||
| - | + | Insights into real-time chemical processes in a calcium sensor protein-directed dynamic library.,Canal-Martin A, Sastre J, Sanchez-Barrena MJ, Canales A, Baldominos S, Pascual N, Martinez-Gonzalez L, Molero D, Fernandez-Valle ME, Saez E, Blanco-Gabella P, Gomez-Rubio E, Martin-Santamaria S, Saiz A, Mansilla A, Canada FJ, Jimenez-Barbero J, Martinez A, Perez-Fernandez R Nat Commun. 2019 Jun 26;10(1):2798. doi: 10.1038/s41467-019-10627-w. PMID:31243268<ref>PMID:31243268</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6qi4" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Blanco-Gabella, P]] | ||
| + | [[Category: Sanchez-Barrena, M J]] | ||
| + | [[Category: Calcium sensor]] | ||
| + | [[Category: Metal binding protein]] | ||
| + | [[Category: Synapse regulation]] | ||
Revision as of 10:49, 17 July 2019
NCS-1 bound to a ligand
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