This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
6ibb
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6ibb is ON HOLD Authors: Haffke, M., Jaakola, V.-P. Description: Crystal structure of the rat isoform of the succinate receptor SUCNR1 (GPR91)in co...) |
|||
| (6 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the rat isoform of the succinate receptor SUCNR1 (GPR91) in complex with a nanobody== | |
| + | <StructureSection load='6ibb' size='340' side='right'caption='[[6ibb]], [[Resolution|resolution]] 2.12Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6ibb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IBB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IBB FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.12Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H95:(2~{S},5~{R})-hexane-2,5-diol'>H95</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</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=6ibb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ibb OCA], [https://pdbe.org/6ibb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ibb RCSB], [https://www.ebi.ac.uk/pdbsum/6ibb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ibb ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SUCR1_RAT SUCR1_RAT] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The tricarboxylic acid cycle intermediate succinate is involved in metabolic processes and plays a crucial role in the homeostasis of mitochondrial reactive oxygen species(1). The receptor responsible for succinate signalling, SUCNR1 (also known as GPR91), is a member of the G-protein-coupled-receptor family(2) and links succinate signalling to renin-induced hypertension, retinal angiogenesis and inflammation(3-5). Because SUCNR1 senses succinate as an immunological danger signal(6)-which has relevance for diseases including ulcerative colitis, liver fibrosis(7), diabetes and rheumatoid arthritis(3,8)-it is of interest as a therapeutic target. Here we report the high-resolution crystal structure of rat SUCNR1 in complex with an intracellular binding nanobody in the inactive conformation. Structure-based mutagenesis and radioligand-binding studies, in conjunction with molecular modelling, identified key residues for species-selective antagonist binding and enabled the determination of the high-resolution crystal structure of a humanized rat SUCNR1 in complex with a high-affinity, human-selective antagonist denoted NF-56-EJ40. We anticipate that these structural insights into the architecture of the succinate receptor and its antagonist selectivity will enable structure-based drug discovery and will further help to elucidate the function of SUCNR1 in vitro and in vivo. | ||
| - | + | Structural basis of species-selective antagonist binding to the succinate receptor.,Haffke M, Fehlmann D, Rummel G, Boivineau J, Duckely M, Gommermann N, Cotesta S, Sirockin F, Freuler F, Littlewood-Evans A, Kaupmann K, Jaakola VP Nature. 2019 Oct;574(7779):581-585. doi: 10.1038/s41586-019-1663-8. Epub 2019 Oct, 23. PMID:31645725<ref>PMID:31645725</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Haffke | + | <div class="pdbe-citations 6ibb" style="background-color:#fffaf0;"></div> |
| - | [[Category: Jaakola | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Rattus norvegicus]] | ||
| + | [[Category: Vicugna pacos]] | ||
| + | [[Category: Haffke M]] | ||
| + | [[Category: Jaakola V-P]] | ||
Current revision
Crystal structure of the rat isoform of the succinate receptor SUCNR1 (GPR91) in complex with a nanobody
| |||||||||||
