4z34: Difference between revisions

Revision as of 07:37, 10 May 2023

Crystal Structure of Human Lysophosphatidic Acid Receptor 1 in complex with ONO9780307

Structural highlights

4z34 is a 1 chain structure with sequence from Escherichia coli and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	1WV, ON7
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LPAR1_HUMAN Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. Seems to be coupled to the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Stimulates phospholipase C (PLC) activity in a manner that is dependent on RALA activation.^[1] C562_ECOLX Electron-transport protein of unknown function.

Publication Abstract from PubMed

Lipid biology continues to emerge as an area of significant therapeutic interest, particularly as the result of an enhanced understanding of the wealth of signaling molecules with diverse physiological properties. This growth in knowledge is epitomized by lysophosphatidic acid (LPA), which functions through interactions with at least six cognate G protein-coupled receptors. Herein, we present three crystal structures of LPA1 in complex with antagonist tool compounds selected and designed through structural and stability analyses. Structural analysis combined with molecular dynamics identified a basis for ligand access to the LPA1 binding pocket from the extracellular space contrasting with the proposed access for the sphingosine 1-phosphate receptor. Characteristics of the LPA1 binding pocket raise the possibility of promiscuous ligand recognition of phosphorylated endocannabinoids. Cell-based assays confirmed this hypothesis, linking the distinct receptor systems through metabolically related ligands with potential functional and therapeutic implications for treatment of disease.

Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1.,Chrencik JE, Roth CB, Terakado M, Kurata H, Omi R, Kihara Y, Warshaviak D, Nakade S, Asmar-Rovira G, Mileni M, Mizuno H, Griffith MT, Rodgers C, Han GW, Velasquez J, Chun J, Stevens RC, Hanson MA Cell. 2015 Jun 18;161(7):1633-43. doi: 10.1016/j.cell.2015.06.002. PMID:26091040^[2]

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

References

↑ Aziziyeh AI, Li TT, Pape C, Pampillo M, Chidiac P, Possmayer F, Babwah AV, Bhattacharya M. Dual regulation of lysophosphatidic acid (LPA1) receptor signalling by Ral and GRK. Cell Signal. 2009 Jul;21(7):1207-17. doi: 10.1016/j.cellsig.2009.03.011. Epub, 2009 Mar 21. PMID:19306925 doi:10.1016/j.cellsig.2009.03.011
↑ Chrencik JE, Roth CB, Terakado M, Kurata H, Omi R, Kihara Y, Warshaviak D, Nakade S, Asmar-Rovira G, Mileni M, Mizuno H, Griffith MT, Rodgers C, Han GW, Velasquez J, Chun J, Stevens RC, Hanson MA. Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1. Cell. 2015 Jun 18;161(7):1633-43. doi: 10.1016/j.cell.2015.06.002. PMID:26091040 doi:https://dx.doi.org/10.1016/j.cell.2015.06.002

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Aziziyeh AI, Li TT, Pape C, Pampillo M, Chidiac P, Possmayer F, Babwah AV, Bhattacharya M. Dual regulation of lysophosphatidic acid (LPA1) receptor signalling by Ral and GRK. Cell Signal. 2009 Jul;21(7):1207-17. doi: 10.1016/j.cellsig.2009.03.011. Epub, 2009 Mar 21. PMID:19306925 doi:10.1016/j.cellsig.2009.03.011

[2] Chrencik JE, Roth CB, Terakado M, Kurata H, Omi R, Kihara Y, Warshaviak D, Nakade S, Asmar-Rovira G, Mileni M, Mizuno H, Griffith MT, Rodgers C, Han GW, Velasquez J, Chun J, Stevens RC, Hanson MA. Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1. Cell. 2015 Jun 18;161(7):1633-43. doi: 10.1016/j.cell.2015.06.002. PMID:26091040 doi:https://dx.doi.org/10.1016/j.cell.2015.06.002

[1]

[2]

@@ Line 3: / Line 3: @@
 <StructureSection load='4z34' size='340' side='right'caption='[[4z34]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4z34]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z34 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Z34 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4z34]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z34 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z34 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1WV:(2S)-2,3-DIHYDROXYPROPYL+(7Z)-TETRADEC-7-ENOATE'>1WV</scene>, <scene name='pdbligand=ON7:{1-[(2S,3S)-2-(2,3-DIHYDRO-1H-INDEN-2-YLMETHYL)-3-(3,5-DIMETHOXY-4-METHYLPHENYL)-3-HYDROXYPROPYL]-4-(METHOXYCARBONYL)-1H-PYRROL-3-YL}ACETIC+ACID'>ON7</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1WV:(2S)-2,3-DIHYDROXYPROPYL+(7Z)-TETRADEC-7-ENOATE'>1WV</scene>, <scene name='pdbligand=ON7:{1-[(2S,3S)-2-(2,3-DIHYDRO-1H-INDEN-2-YLMETHYL)-3-(3,5-DIMETHOXY-4-METHYLPHENYL)-3-HYDROXYPROPYL]-4-(METHOXYCARBONYL)-1H-PYRROL-3-YL}ACETIC+ACID'>ON7</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4z35|4z35]], [[4z36|4z36]]</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=4z34 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z34 OCA], [https://pdbe.org/4z34 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z34 RCSB], [https://www.ebi.ac.uk/pdbsum/4z34 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z34 ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LPAR1, EDG2, LPA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=4z34 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z34 OCA], [http://pdbe.org/4z34 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4z34 RCSB], [http://www.ebi.ac.uk/pdbsum/4z34 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4z34 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/LPAR1_HUMAN LPAR1_HUMAN]] Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. Seems to be coupled to the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Stimulates phospholipase C (PLC) activity in a manner that is dependent on RALA activation.<ref>PMID:19306925</ref>
+[https://www.uniprot.org/uniprot/LPAR1_HUMAN LPAR1_HUMAN] Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. Seems to be coupled to the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Stimulates phospholipase C (PLC) activity in a manner that is dependent on RALA activation.<ref>PMID:19306925</ref> [https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 21: @@
 ==See Also==
 *[[Lysophosphatidic acid receptor|Lysophosphatidic acid receptor]]
+*[[Sandbox Reserved 1789|Sandbox Reserved 1789]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Bacillus coli migula 1895]]
+[[Category: Escherichia coli]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Asmar-Rovira, G]]
+[[Category: Asmar-Rovira G]]
-[[Category: Chrencik, J E]]
+[[Category: Chrencik JE]]
-[[Category: Chun, J]]
+[[Category: Chun J]]
-[[Category: GPCR, GPCR Network]]
+[[Category: Griffith MT]]
-[[Category: Griffith, M T]]
+[[Category: Han GW]]
-[[Category: Han, G W]]
+[[Category: Hanson MA]]
-[[Category: Hanson, M A]]
+[[Category: Kihara Y]]
-[[Category: Kihara, Y]]
+[[Category: Kurata H]]
-[[Category: Kurata, H]]
+[[Category: Mileni M]]
-[[Category: Mileni, M]]
+[[Category: Mizuno H]]
-[[Category: Mizuno, H]]
+[[Category: Nakade S]]
-[[Category: Nakade, S]]
+[[Category: Omi R]]
-[[Category: Omi, R]]
+[[Category: Rodgers C]]
-[[Category: Rodgers, C]]
+[[Category: Roth CB]]
-[[Category: Roth, C B]]
+[[Category: Stevens RC]]
-[[Category: Stevens, R C]]
+[[Category: Terakado M]]
-[[Category: Terakado, M]]
+[[Category: Velasquez J]]
-[[Category: Velasquez, J]]
+[[Category: Warshaviak D]]
-[[Category: Warshaviak, D]]
-[[Category: Antagonist]]
-[[Category: Compound design]]
-[[Category: Endogenous ligand]]
-[[Category: Gpcr network]]
-[[Category: Lipid receptor]]
-[[Category: Membrane protein]]
-[[Category: Polypharmacology]]
-[[Category: Psi-biology]]
-[[Category: Structural genomic]]
-[[Category: Transport protein-inhibitor complex]]

4z34: Difference between revisions

Revision as of 07:37, 10 May 2023

Crystal Structure of Human Lysophosphatidic Acid Receptor 1 in complex with ONO9780307

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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