4xhd: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 3: / Line 3: @@
 <StructureSection load='4xhd' size='340' side='right'caption='[[4xhd]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4xhd]] is a 1 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=4XHD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XHD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4xhd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XHD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XHD FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=40U:N-{(2R)-1-[(4S)-4-(4-CHLOROPHENYL)-4-HYDROXY-3,3-DIMETHYLPIPERIDIN-1-YL]-3-METHYL-1-OXOBUTAN-2-YL}-2-CYCLOPROPYLACETAMIDE'>40U</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR1I2, PXR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=40U:N-{(2R)-1-[(4S)-4-(4-CHLOROPHENYL)-4-HYDROXY-3,3-DIMETHYLPIPERIDIN-1-YL]-3-METHYL-1-OXOBUTAN-2-YL}-2-CYCLOPROPYLACETAMIDE'>40U</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=4xhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xhd OCA], [http://pdbe.org/4xhd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xhd RCSB], [http://www.ebi.ac.uk/pdbsum/4xhd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xhd ProSAT]</span></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=4xhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xhd OCA], [https://pdbe.org/4xhd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xhd RCSB], [https://www.ebi.ac.uk/pdbsum/4xhd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xhd ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/NR1I2_HUMAN NR1I2_HUMAN]] Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.<ref>PMID:9727070</ref> <ref>PMID:11668216</ref> <ref>PMID:11297522</ref> <ref>PMID:19297428</ref> <ref>PMID:12578355</ref> <ref>PMID:18768384</ref>
+[https://www.uniprot.org/uniprot/NR1I2_HUMAN NR1I2_HUMAN] Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.<ref>PMID:9727070</ref> <ref>PMID:11668216</ref> <ref>PMID:11297522</ref> <ref>PMID:19297428</ref> <ref>PMID:12578355</ref> <ref>PMID:18768384</ref>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-The human pregnane X receptor (PXR) is a promiscuous nuclear receptor that functions as a sensor to a wide variety of xenobiotics and regulates expression of several drug metabolizing enzymes and transporters. We have generated "Adnectins", derived from 10th fibronectin type III domain (10Fn3), that target the PXR ligand binding domain (LBD) interactions with the steroid receptor co-activator-1 (SRC-1) peptide, displacing SRC-1 binding. Adnectins are structurally homologous to the immunoglobulin superfamily. Three different co-crystal structures of PXR LBD with Adnectin-1 and CCR1 (CC chemokine receptor-1) antagonist Compound-1 were determined. This structural information was used to modulate PXR affinity for a related CCR1 antagonist compound that entered into clinical trials for rheumatoid arthritis. The structures of PXR with Adnectin-1 reveal specificity of Adnectin-1 in not only targeting the interface of the SRC-1 interactions but also engaging the same set of residues that are involved in binding of SRC-1 to PXR. Substituting SRC-1 with Adnectin-1 does not alter the binding conformation of Compound-1 in the ligand binding pocket. The structure also reveals the possibility of using Adnectins as crystallization chaperones to generate structures of PXR with compounds of interest.
-Developing Adnectins That Target SRC Co-Activator Binding to PXR: A Structural Approach toward Understanding Promiscuity of PXR.,Khan JA, Camac DM, Low S, Tebben AJ, Wensel DL, Wright MC, Su J, Jenny V, Gupta RD, Ruzanov M, Russo KA, Bell A, An Y, Bryson JW, Gao M, Gambhire P, Baldwin ET, Gardner D, Cavallaro CL, Duncia JV, Hynes J Jr J Mol Biol. 2015 Jan 8. pii: S0022-2836(15)00002-9. doi:, 10.1016/j.jmb.2014.12.022. PMID:25579995<ref>PMID:25579995</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 4xhd" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Pregnane X receptor|Pregnane X receptor]]
+*[[Pregnane X receptor 3D structures|Pregnane X receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Camac, D M]]
+[[Category: Camac DM]]
-[[Category: Khan, J A]]
+[[Category: Khan JA]]
-[[Category: Activation function]]
-[[Category: Adnectin nr]]
-[[Category: Af]]
-[[Category: Ccr1]]
-[[Category: Chemokine receptor-1]]
-[[Category: Cyp]]
-[[Category: Cytochrome p450]]
-[[Category: Ligand binding domain]]
-[[Category: Mdr1]]
-[[Category: Multi-drug resistance gene-1]]
-[[Category: Nuclear receptor]]
-[[Category: Pregnane x receptor]]
-[[Category: Pxr]]
-[[Category: Steroid receptor coactivator-1]]
-[[Category: Transcription]]