View source for 5q0s


==Ligand binding to FARNESOID-X-RECEPTOR==
<StructureSection load='5q0s' size='340' side='right' caption='[[5q0s]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5q0s]] 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=5Q0S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Q0S FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9LJ:(2S)-2-[2-(4-chlorophenyl)-5,6-difluoro-1H-benzimidazol-1-yl]-N-(2-cyanophenyl)-2-cyclohexylacetamide'>9LJ</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR1H4, BAR, FXR, HRR1, RIP14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5q0s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5q0s OCA], [http://pdbe.org/5q0s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5q0s RCSB], [http://www.ebi.ac.uk/pdbsum/5q0s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5q0s ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/NR1H4_HUMAN NR1H4_HUMAN]] Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.<ref>PMID:10334992</ref> <ref>PMID:10334993</ref> <ref>PMID:12815072</ref> <ref>PMID:15471871</ref> <ref>PMID:12718892</ref> <ref>PMID:18621523</ref> <ref>PMID:19410460</ref> <ref>PMID:19586769</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Drug Design Data Resource (D3R) ran Grand Challenge 2 (GC2) from September 2016 through February 2017. This challenge was based on a dataset of structures and affinities for the nuclear receptor farnesoid X receptor (FXR), contributed by F. Hoffmann-La Roche. The dataset contained 102 IC50 values, spanning six orders of magnitude, and 36 high-resolution co-crystal structures with representatives of four major ligand classes. Strong global participation was evident, with 49 participants submitting 262 prediction submission packages in total. Procedurally, GC2 mimicked Grand Challenge 2015 (GC2015), with a Stage 1 subchallenge testing ligand pose prediction methods and ranking and scoring methods, and a Stage 2 subchallenge testing only ligand ranking and scoring methods after the release of all blinded co-crystal structures. Two smaller curated sets of 18 and 15 ligands were developed to test alchemical free energy methods. This overview summarizes all aspects of GC2, including the dataset details, challenge procedures, and participant results. We also consider implications for progress in the field, while highlighting methodological areas that merit continued development. Similar to GC2015, the outcome of GC2 underscores the pressing need for methods development in pose prediction, particularly for ligand scaffolds not currently represented in the Protein Data Bank ( http://www.pdb.org ), and in affinity ranking and scoring of bound ligands.

D3R Grand Challenge 2: blind prediction of protein-ligand poses, affinity rankings, and relative binding free energies.,Gaieb Z, Liu S, Gathiaka S, Chiu M, Yang H, Shao C, Feher VA, Walters WP, Kuhn B, Rudolph MG, Burley SK, Gilson MK, Amaro RE J Comput Aided Mol Des. 2017 Dec 4. pii: 10.1007/s10822-017-0088-4. doi:, 10.1007/s10822-017-0088-4. PMID:29204945<ref>PMID:29204945</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5q0s" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Benz, J]]
[[Category: Burger, D]]
[[Category: Burley, S K]]
[[Category: Joseph, C]]
[[Category: Kuhn, B]]
[[Category: Rudolph, M G]]
[[Category: Ruf, A]]
[[Category: Shao, C]]
[[Category: Thoma, R]]
[[Category: Yang, H]]
[[Category: D3r]]
[[Category: Docking]]
[[Category: Fxr]]
[[Category: Transcription]]