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6b5v

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Revision as of 23:16, 10 April 2020

Structure of TRPV5 in complex with econazole

6b5v, resolution 4.80Å

Structural highlights

6b5v is a 4 chain structure with sequence from European rabbit. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	Trpv5, Ecac1 (European rabbit)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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]^[1] ^[2] ^[3]

Publication Abstract from PubMed

The transient receptor potential vanilloid 5 (TRPV5) channel is a member of the transient receptor potential (TRP) channel family, which is highly selective for Ca(2+), that is present primarily at the apical membrane of distal tubule epithelial cells in the kidney and plays a key role in Ca(2+) reabsorption. Here we present the structure of the full-length rabbit TRPV5 channel as determined using cryo-EM in complex with its inhibitor econazole. This structure reveals that econazole resides in a hydrophobic pocket analogous to that occupied by phosphatidylinositides and vanilloids in TRPV1, thus suggesting conserved mechanisms for ligand recognition and lipid binding among TRPV channels. The econazole-bound TRPV5 structure adopts a closed conformation with a distinct lower gate that occludes Ca(2+) permeation through the channel. Structural comparisons between TRPV5 and other TRPV channels, complemented with molecular dynamics (MD) simulations of the econazole-bound TRPV5 structure, allowed us to gain mechanistic insight into TRPV5 channel inhibition by small molecules.

Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM.,Hughes TET, Lodowski DT, Huynh KW, Yazici A, Del Rosario J, Kapoor A, Basak S, Samanta A, Han X, Chakrapani S, Zhou ZH, Filizola M, Rohacs T, Han S, Moiseenkova-Bell VY Nat Struct Mol Biol. 2018 Jan;25(1):53-60. doi: 10.1038/s41594-017-0009-1. Epub, 2018 Jan 1. PMID:29323279^[4]

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

References

↑ Hoenderop JG, van der Kemp AW, Hartog A, van de Graaf SF, van Os CH, Willems PH, Bindels RJ. Molecular identification of the apical Ca2+ channel in 1, 25-dihydroxyvitamin D3-responsive epithelia. J Biol Chem. 1999 Mar 26;274(13):8375-8. PMID:10085067
↑ Nilius B, Vennekens R, Prenen J, Hoenderop JG, Droogmans G, Bindels RJ. The single pore residue Asp542 determines Ca2+ permeation and Mg2+ block of the epithelial Ca2+ channel. J Biol Chem. 2001 Jan 12;276(2):1020-5. PMID:11035011 doi:http://dx.doi.org/10.1074/jbc.M006184200
↑ Hoenderop JG, Voets T, Hoefs S, Weidema F, Prenen J, Nilius B, Bindels RJ. Homo- and heterotetrameric architecture of the epithelial Ca2+ channels TRPV5 and TRPV6. EMBO J. 2003 Feb 17;22(4):776-85. PMID:12574114 doi:http://dx.doi.org/10.1093/emboj/cdg080
↑ Hughes TET, Lodowski DT, Huynh KW, Yazici A, Del Rosario J, Kapoor A, Basak S, Samanta A, Han X, Chakrapani S, Zhou ZH, Filizola M, Rohacs T, Han S, Moiseenkova-Bell VY. Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM. Nat Struct Mol Biol. 2018 Jan;25(1):53-60. doi: 10.1038/s41594-017-0009-1. Epub, 2018 Jan 1. PMID:29323279 doi:http://dx.doi.org/10.1038/s41594-017-0009-1

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/6b5v"

@@ Line 3: / Line 3: @@
 <SX load='6b5v' size='340' side='right' viewer='molstar' caption='[[6b5v]], [[Resolution|resolution]] 4.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6b5v]] 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=6B5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B5V FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6b5v]] 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=6B5V OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6B5V FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ECL:1-[(2R)-2-[(4-CHLOROBENZYL)OXY]-2-(2,4-DICHLOROPHENYL)ETHYL]-1H-IMIDAZOLE'>ECL</scene></td></tr>
+</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=ECL:1-[(2R)-2-[(4-CHLOROBENZYL)OXY]-2-(2,4-DICHLOROPHENYL)ETHYL]-1H-IMIDAZOLE'>ECL</scene></td></tr>
 <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>
-<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=6b5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b5v OCA], [http://pdbe.org/6b5v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b5v RCSB], [http://www.ebi.ac.uk/pdbsum/6b5v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b5v ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6b5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b5v OCA], [http://pdbe.org/6b5v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b5v RCSB], [http://www.ebi.ac.uk/pdbsum/6b5v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b5v ProSAT]</span></td></tr>
 </table>
 == Function ==

6b5v

From Proteopedia

Revision as of 23:16, 10 April 2020

Structure of TRPV5 in complex with econazole

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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