6pbe

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Current revision (09:26, 20 March 2024) (edit) (undo)
 
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<SX load='6pbe' size='340' side='right' viewer='molstar' caption='[[6pbe]], [[Resolution|resolution]] 3.78&Aring;' scene=''>
<SX load='6pbe' size='340' side='right' viewer='molstar' caption='[[6pbe]], [[Resolution|resolution]] 3.78&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6pbe]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PBE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PBE FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6pbe]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PBE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PBE FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=O6S:(4-oxo-5-phenyl-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)methyl+3-(3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propanoate'>O6S</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.78&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Trpv5, Ecac1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=O6S:(4-oxo-5-phenyl-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)methyl+3-(3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propanoate'>O6S</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6pbe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pbe OCA], [http://pdbe.org/6pbe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pbe RCSB], [http://www.ebi.ac.uk/pdbsum/6pbe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pbe ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6pbe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pbe OCA], [https://pdbe.org/6pbe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pbe RCSB], [https://www.ebi.ac.uk/pdbsum/6pbe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pbe ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/TRPV5_RABIT TRPV5_RABIT]] Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine (PubMed:12574114). Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules (By similarity). The channel is activated by low internal calcium level and the current exhibits an inward rectification (By similarity). A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay (By similarity). Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (PubMed:12574114).[UniProtKB:P69744][UniProtKB:Q9NQA5]<ref>PMID:10085067</ref> <ref>PMID:11035011</ref> <ref>PMID:12574114</ref>
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[https://www.uniprot.org/uniprot/TRPV5_RABIT TRPV5_RABIT] Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine (PubMed:12574114). Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules (By similarity). The channel is activated by low internal calcium level and the current exhibits an inward rectification (By similarity). A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay (By similarity). Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (PubMed:12574114).[UniProtKB:P69744][UniProtKB:Q9NQA5]<ref>PMID:10085067</ref> <ref>PMID:11035011</ref> <ref>PMID:12574114</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Transient receptor potential vanilloid 5 (TRPV5) is a highly calcium selective ion channel that acts as the rate-limiting step of calcium reabsorption in the kidney. The lack of potent, specific modulators of TRPV5 has limited the ability to probe the contribution of TRPV5 in disease phenotypes such as hypercalcemia and nephrolithiasis. Here, we performed structure-based virtual screening (SBVS) at a previously identified TRPV5 inhibitor binding site coupled with electrophysiology screening and identified three novel inhibitors of TRPV5, one of which exhibits high affinity, and specificity for TRPV5 over other TRP channels, including its close homologue TRPV6. Cryo-electron microscopy of TRPV5 in the presence of the specific inhibitor and its parent compound revealed novel binding sites for this channel. Structural and functional analysis have allowed us to suggest a mechanism of action for the selective inhibition of TRPV5 and lay the groundwork for rational design of new classes of TRPV5 modulators.
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Structure-based characterization of novel TRPV5 inhibitors.,Hughes TE, Del Rosario JS, Kapoor A, Yazici AT, Yudin Y, Fluck EC, Filizola M, Rohacs T, Moiseenkova-Bell VY Elife. 2019 Oct 24;8. pii: 49572. doi: 10.7554/eLife.49572. PMID:31647410<ref>PMID:31647410</ref>
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==See Also==
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*[[Ion channels 3D structures|Ion channels 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6pbe" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
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__TOC__
</SX>
</SX>
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[[Category: European rabbit]]
 
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Filizola, M]]
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[[Category: Oryctolagus cuniculus]]
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[[Category: Fluck, E C]]
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[[Category: Filizola M]]
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[[Category: Hughes, T E.T]]
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[[Category: Fluck EC]]
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[[Category: Kapoor, A]]
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[[Category: Hughes TET]]
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[[Category: Moiseenkova-Bell, V Y]]
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[[Category: Kapoor A]]
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[[Category: Rohacs, T]]
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[[Category: Moiseenkova-Bell VY]]
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[[Category: Rosario, J S.D]]
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[[Category: Rohacs T]]
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[[Category: Yazici, A T]]
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[[Category: Rosario JSD]]
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[[Category: Calcium channel]]
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[[Category: Yazici AT]]
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[[Category: Inhibitor]]
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[[Category: Transport protein]]
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[[Category: Trp channel]]
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[[Category: Trpv5]]
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Current revision

ZINC17988990-bound TRPV5 in nanodiscs

6pbe, resolution 3.78Å

Proteopedia Page Contributors and Editors (what is this?)

OCA

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