9jo4

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: '''Unreleased structure''' The entry 9jo4 is ON HOLD Authors: Kim, S., Park, S., Lee, N.Y., Lee, E.Y., Lee, N., Roh, E.C., Kim, Y.G., Kim, H.J., Jin, M.S., Park, C.S., Kim, Y.C. Descri...)
Current revision (19:21, 26 February 2025) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 9jo4 is ON HOLD
+
==Cryo-EM structure of human BKca channel-compound 51b complex==
 +
<StructureSection load='9jo4' size='340' side='right'caption='[[9jo4]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[9jo4]] is a 4 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=9JO4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9JO4 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]] 3.4&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1L4F:5-(5-morpholin-4-ylpentylamino)-2-[2,3,5,6-tetrakis(fluoranyl)-4-(trifluoromethyl)phenoxy]phenol'>A1L4F</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=9jo4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9jo4 OCA], [https://pdbe.org/9jo4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9jo4 RCSB], [https://www.ebi.ac.uk/pdbsum/9jo4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9jo4 ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/KCMA1_HUMAN KCMA1_HUMAN]
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
The BK(Ca) channel, a large-conductance calcium-activated potassium channel, plays a crucial role in maintaining the homeostasis of the micturition cycle and airway-related functions. In this study, we optimized a novel BK(Ca) channel activator, 4d, with a diphenyl ether structure identified from library screening. This led to the discovery of potent activators, 10b (EC(50) = 0.12 muM, cell-based assay) and 51b, an orally bioavailable derivative. Compound 10b demonstrated potent in vivo efficacy in a spontaneous hypertensive rat (SHR) of urinary incontinence model, while compound 51b showed dose-dependent cough suppression efficacy with an ED(50) of 11.8 mg/kg in a citric acid-induced cough model. Furthermore, we reported the cryo-electron microscopy (cryo-EM) structures of the BK(Ca) channel in complex with 10b and 51b at resolutions of 2.8 and 3.4 A. Based on structural analyses, we determined the binding sites and key interaction residues of 51b, which were validated via mutation studies.
-
Authors: Kim, S., Park, S., Lee, N.Y., Lee, E.Y., Lee, N., Roh, E.C., Kim, Y.G., Kim, H.J., Jin, M.S., Park, C.S., Kim, Y.C.
+
Discovery of Diphenyl Ether Derivatives as Novel BK(Ca) Channel Activators: Structure-Activity Relationship, Cryo-EM Complex Structures, and In Vivo Animal Studies.,Park SB, Lee NY, Lee EY, Kim S, Lee N, Roh EC, Kim YG, Kim HJ, Jin MS, Park CS, Kim YC J Med Chem. 2025 Feb 13. doi: 10.1021/acs.jmedchem.4c02008. PMID:39947888<ref>PMID:39947888</ref>
-
Description: Cryo-EM structure of human BKca channel-compound 51b complex
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
-
[[Category: Park, C.S]]
+
<div class="pdbe-citations 9jo4" style="background-color:#fffaf0;"></div>
-
[[Category: Kim, Y.C]]
+
== References ==
-
[[Category: Kim, Y.G]]
+
<references/>
-
[[Category: Lee, N]]
+
__TOC__
-
[[Category: Lee, N.Y]]
+
</StructureSection>
-
[[Category: Kim, S]]
+
[[Category: Homo sapiens]]
-
[[Category: Park, S]]
+
[[Category: Large Structures]]
-
[[Category: Roh, E.C]]
+
[[Category: Jin MS]]
-
[[Category: Lee, E.Y]]
+
[[Category: Kim HJ]]
-
[[Category: Kim, H.J]]
+
[[Category: Kim S]]
-
[[Category: Jin, M.S]]
+
[[Category: Kim YC]]
 +
[[Category: Kim YG]]
 +
[[Category: Lee EY]]
 +
[[Category: Lee N]]
 +
[[Category: Lee NY]]
 +
[[Category: Park CS]]
 +
[[Category: Park S]]
 +
[[Category: Roh EC]]

Current revision

Cryo-EM structure of human BKca channel-compound 51b complex

PDB ID 9jo4

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9jo4"
Personal tools