View source for 6ibb


==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]] 2.12&Aring;' 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]] 2.12&#8491;</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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ibb" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Vicugna pacos]]
[[Category: Haffke M]]
[[Category: Jaakola V-P]]