6p9f
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of RAR-related orphan receptor C (NHIS-RORGT(244-487)-L6-SRC1(678-692)) in complex with a phenyl (3-phenylpyrrolidin-3-yl)sulfone inhibitor== | |
| + | <StructureSection load='6p9f' size='340' side='right'caption='[[6p9f]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6p9f]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P9F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P9F FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=O5A:trans-4-{(3R)-3-[(4-fluorophenyl)sulfonyl]-3-[4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)phenyl]pyrrolidine-1-carbonyl}cyclohexane-1-carboxylic+acid'>O5A</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </span></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=6p9f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p9f OCA], [http://pdbe.org/6p9f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p9f RCSB], [http://www.ebi.ac.uk/pdbsum/6p9f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p9f ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/RORG_HUMAN RORG_HUMAN]] Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | An X-ray crystal structure of one of our previously discovered RORgammat inverse agonists bound to the RORgammat ligand binding domain revealed that the cyclohexane carboxylic acid group of compound 2 plays a significant role in RORgammat binding, forming four hydrogen bonding and ionic interactions with RORgammat. SAR studies centered around the cyclohexane carboxylic acid group led to identification of several structurally diverse and more potent compounds, including new carboxylic acid analogues 7 and 20, and cyclic sulfone analogues 34 and 37. Notably, compounds 7 and 20 were found to maintain the desirable pharmacokinetic profile of 2. | ||
| - | + | Identification of potent, selective and orally bioavailable phenyl ((R)-3-phenylpyrrolidin-3-yl)sulfone analogues as RORgammat inverse agonists.,Lu Z, Duan JJ, Xiao H, Neels J, Wu DR, Weigelt CA, Sack JS, Khan J, Ruzanov M, An Y, Yarde M, Karmakar A, Vishwakrishnan S, Baratam V, Shankarappa H, Vanteru S, Babu V, Basha M, Kumar Gupta A, Kumaravel S, Mathur A, Zhao Q, Salter-Cid LM, Carter PH, Murali Dhar TG Bioorg Med Chem Lett. 2019 Jun 20. pii: S0960-894X(19)30416-0. doi:, 10.1016/j.bmcl.2019.06.036. PMID:31257087<ref>PMID:31257087</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6p9f" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Histone acetyltransferase]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Sack, J]] | [[Category: Sack, J]] | ||
| + | [[Category: Inve agonist]] | ||
| + | [[Category: Ligand-binding domain]] | ||
| + | [[Category: Nuclear hormone receptor]] | ||
| + | [[Category: Rorgt]] | ||
| + | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 10:49, 17 July 2019
Crystal structure of RAR-related orphan receptor C (NHIS-RORGT(244-487)-L6-SRC1(678-692)) in complex with a phenyl (3-phenylpyrrolidin-3-yl)sulfone inhibitor
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