7e4t: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 3: / Line 3: @@
 <StructureSection load='7e4t' size='340' side='right'caption='[[7e4t]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7e4t]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E4T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E4T FirstGlance]. <br>
+<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E4T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E4T FirstGlance]. <br>
-</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=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene>, <scene name='pdbligand=PTY:PHOSPHATIDYLETHANOLAMINE'>PTY</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene>, <scene name='pdbligand=YZY:(2S)-2-(HEXADECANOYLOXY)-3-HYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>YZY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRPC5, TRP5 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene>, <scene name='pdbligand=PTY:PHOSPHATIDYLETHANOLAMINE'>PTY</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene>, <scene name='pdbligand=YZY:(2S)-2-(HEXADECANOYLOXY)-3-HYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>YZY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7e4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e4t OCA], [https://pdbe.org/7e4t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e4t RCSB], [https://www.ebi.ac.uk/pdbsum/7e4t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e4t ProSAT]</span></td></tr>
 </table>
-== Function ==
-[[https://www.uniprot.org/uniprot/TRPC5_HUMAN TRPC5_HUMAN]] Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Has also been shown to be calcium-selective (By similarity). May also be activated by intracellular calcium store depletion. Mediates calcium-dependent phosphatidylserine externalization and apoptosis in neurons via its association with PLSCR1 (By similarity).[UniProtKB:Q9QX29]<ref>PMID:16284075</ref>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-TRPC5 channel is a nonselective cation channel that participates in diverse physiological processes. TRPC5 inhibitors show promise in the treatment of anxiety disorder, depression, and kidney disease. However, the binding sites and inhibitory mechanism of TRPC5 inhibitors remain elusive. Here, we present the cryo-EM structures of human TRPC5 in complex with two distinct inhibitors, namely clemizole and HC-070, to the resolution of 2.7 A. The structures reveal that clemizole binds inside the voltage sensor-like domain of each subunit. In contrast, HC-070 is wedged between adjacent subunits and replaces the glycerol group of a putative diacylglycerol molecule near the extracellular side. Moreover, we found mutations in the inhibitor binding pockets altered the potency of inhibitors. These structures suggest that both clemizole and HC-070 exert the inhibitory functions by stabilizing the ion channel in a nonconductive closed state. These results pave the way for further design and optimization of inhibitors targeting human TRPC5.
-Structural basis for human TRPC5 channel inhibition by two distinct inhibitors.,Song K, Wei M, Guo W, Quan L, Kang Y, Wu JX, Chen L Elife. 2021 Mar 8;10. pii: 63429. doi: 10.7554/eLife.63429. PMID:33683200<ref>PMID:33683200</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 7e4t" style="background-color:#fffaf0;"></div>
-== References ==
-<references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Chen, L]]
+[[Category: Chen L]]
-[[Category: Guo, W]]
+[[Category: Guo W]]
-[[Category: Song, K]]
+[[Category: Song K]]
-[[Category: Wei, M]]
+[[Category: Wei M]]
-[[Category: Metal transport]]
-[[Category: Trpc]]
-[[Category: Trpc5]]