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| <StructureSection load='6ysn' size='340' side='right'caption='[[6ysn]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='6ysn' size='340' side='right'caption='[[6ysn]], [[Resolution|resolution]] 3.00Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6ysn]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YSN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YSN FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YSN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YSN FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PJQ:7-[(4-chlorophenyl)methyl]-3-methyl-1-(3-oxidanylpropyl)-8-[3-(trifluoromethyloxy)phenoxy]purine-2,6-dione'>PJQ</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]] 3Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRPC5, TRP5 ([http://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=PJQ:7-[(4-chlorophenyl)methyl]-3-methyl-1-(3-oxidanylpropyl)-8-[3-(trifluoromethyloxy)phenoxy]purine-2,6-dione'>PJQ</scene></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=6ysn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ysn OCA], [http://pdbe.org/6ysn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ysn RCSB], [http://www.ebi.ac.uk/pdbsum/6ysn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ysn ProSAT]</span></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=6ysn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ysn OCA], [https://pdbe.org/6ysn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ysn RCSB], [https://www.ebi.ac.uk/pdbsum/6ysn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ysn ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function ==
| |
| [[http://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI]] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
| |
| TRPC1/4/5 channels are non-specific cation channels implicated in a wide variety of diseases, and TRPC1/4/5 inhibitors have recently entered clinical trials. However, fundamental and translational studies require a better understanding of TRPC1/4/5 channel regulation by endogenous and exogenous factors. Although several potent and selective TRPC1/4/5 modulators have been reported, the paucity of mechanistic insights into their modes-of-action remains a barrier to the development of new chemical probes and drug candidates. Xanthine-based modulators include the most potent and selective TRPC1/4/5 inhibitors described to date, as well as TRPC5 activators. Our previous studies suggest that xanthines interact with a, so far, elusive pocket of TRPC1/4/5 channels that is essential to channel gating. Here we report the structure of a small-molecule-bound TRPC1/4/5 channel-human TRPC5 in complex with the xanthine Pico145-to 3.0 A. We found that Pico145 binds to a conserved lipid binding site of TRPC5, where it displaces a bound phospholipid. Our findings explain the mode-of-action of xanthine-based TRPC1/4/5 modulators, and suggest a structural basis for TRPC1/4/5 modulation by endogenous factors such as (phospho)lipids and Zn(2+) ions. These studies lay the foundations for the structure-based design of new generations of TRPC1/4/5 modulators.
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| Human TRPC5 structures reveal interaction of a xanthine-based TRPC1/4/5 inhibitor with a conserved lipid binding site.,Wright DJ, Simmons KJ, Johnson RM, Beech DJ, Muench SP, Bon RS Commun Biol. 2020 Nov 23;3(1):704. doi: 10.1038/s42003-020-01437-8. PMID:33230284<ref>PMID:33230284</ref>
| | ==See Also== |
| | | *[[Maltose-binding protein 3D structures|Maltose-binding protein 3D structures]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6ysn" style="background-color:#fffaf0;"></div>
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| == References ==
| |
| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]]
| |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Bon, R S]] | | [[Category: Bon RS]] |
| [[Category: Johnson, R M]] | | [[Category: Johnson RM]] |
| [[Category: Muench, S P]] | | [[Category: Muench SP]] |
| [[Category: Wright, D J]] | | [[Category: Wright DJ]] |
| [[Category: Inhibitor]]
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| [[Category: Ion channel]]
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| [[Category: Membrane protein]]
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| [[Category: Small molecule]]
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| [[Category: Tetramer]]
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