6qi4

From Proteopedia

(Difference between revisions)

Current revision

NCS-1 bound to a ligand

Structural highlights

6qi4 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.78Å
Ligands:	, , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).

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^[1]

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

References

↑ 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. Insights into real-time chemical processes in a calcium sensor protein-directed dynamic library. Nat Commun. 2019 Jun 26;10(1):2798. doi: 10.1038/s41467-019-10627-w. PMID:31243268 doi:http://dx.doi.org/10.1038/s41467-019-10627-w

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6qi4"

Categories: Homo sapiens | Large Structures | Blanco-Gabella P | Sanchez-Barrena MJ

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6qi4 is ON HOLD  until Paper Publication
+==NCS-1 bound to a ligand==
+<StructureSection load='6qi4' size='340' side='right'caption='[[6qi4]], [[Resolution|resolution]] 1.78&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6qi4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/fgij/fg.htm?mol=6QI4 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]] 1.78&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[https://proteopedia.org/fgij/fg.htm?mol=6qi4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qi4 OCA], [https://pdbe.org/6qi4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qi4 RCSB], [https://www.ebi.ac.uk/pdbsum/6qi4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qi4 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://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.
-Authors:
+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>
-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 6qi4" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Blanco-Gabella P]]
+[[Category: Sanchez-Barrena MJ]]

6qi4

From Proteopedia

Current revision

NCS-1 bound to a ligand

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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