3c6p: Difference between revisions

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-{{Seed}}
-[[Image:3c6p.png|left|200px]]
-<!--
+==Small molecule agonists and antagonists of F-box protein-substrate interactions in auxin perception and signaling==
-The line below this paragraph, containing "STRUCTURE_3c6p", creates the "Structure Box" on the page.
+<StructureSection load='3c6p' size='340' side='right'caption='[[3c6p]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3c6p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C6P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C6P FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2S3:(2S)-2-(1H-INDOL-3-YL)PENTANOIC+ACID'>2S3</scene>, <scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene></td></tr>
-{{STRUCTURE_3c6p|  PDB=3c6p  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3c6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c6p OCA], [https://pdbe.org/3c6p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c6p RCSB], [https://www.ebi.ac.uk/pdbsum/3c6p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c6p ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/SKP1A_ARATH SKP1A_ARATH] Involved in ubiquitination and subsequent proteasomal degradation of target proteins. Together with CUL1, RBX1 and a F-box protein, it forms a SCF E3 ubiquitin ligase complex. The functional specificity of this complex depends of the type of F-box protein. In the SCF complex, it serves as an adapter that links the F-box protein to CUL1. SCF(UFO) is required for vegetative and floral organ development as well as for male gametogenesis. SCF(TIR1) is involved in auxin signaling pathway. SCF(COI1) regulates responses to jasmonates. SCF(EID1) and SCF(AFR) are implicated in phytochrome A light signaling. SCF(ADO1), SCF(ADO2), SCF(ADO3) are related to the circadian clock. SCF(ORE9) seems to be involved in senescence. SCF(EBF1/EBF2) may regulate ethylene signaling. Plays a role during embryogenesis and early postembryonic development, especially during cell elongation and division. Contributes to the correct chromosome segregation during tetrad formation.<ref>PMID:10528262</ref> <ref>PMID:10398681</ref> <ref>PMID:10500191</ref> <ref>PMID:11526079</ref> <ref>PMID:12970487</ref> <ref>PMID:14688296</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c6/3c6p_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3c6p ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The regulation of gene expression by the hormone auxin is a crucial mechanism in plant development. We have shown that the Arabidopsis F-box protein TIR1 is a receptor for auxin, and our recent structural work has revealed the molecular mechanism of auxin perception. TIR1 is the substrate receptor of the ubiquitin-ligase complex SCF(TIR1). Auxin binding enhances the interaction between TIR1 and its substrates, the Aux/IAA repressors, thereby promoting the ubiquitination and degradation of Aux/IAAs, altering the expression of hundreds of genes. TIR1 is the prototype of a new class of hormone receptor and the first example of an SCF ubiquitin-ligase modulated by a small molecule. Here, we describe the design, synthesis, and characterization of a series of auxin agonists and antagonists. We show these molecules are specific to TIR1-mediated events in Arabidopsis, and their mode of action in binding to TIR1 is confirmed by x-ray crystallographic analysis. Further, we demonstrate the utility of these probes for the analysis of TIR1-mediated auxin signaling in the moss Physcomitrella patens. Our work not only provides a useful tool for plant chemical biology but also demonstrates an example of a specific small-molecule inhibitor of F-box protein-substrate recruitment. Substrate recognition and subsequent ubiquitination by SCF-type ubiquitin ligases are central to many cellular processes in eukaryotes, and ubiquitin-ligase function is affected in several human diseases. Our work supports the idea that it may be possible to design small-molecule agents to modulate ubiquitin-ligase function therapeutically.
-===Small molecule agonists and antagonists of F-box protein-substrate interactions in auxin perception and signaling===
+Small-molecule agonists and antagonists of F-box protein-substrate interactions in auxin perception and signaling.,Hayashi K, Tan X, Zheng N, Hatate T, Kimura Y, Kepinski S, Nozaki H Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5632-7. Epub 2008 Apr 7. PMID:18391211<ref>PMID:18391211</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3c6p" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_18391211}}, adds the Publication Abstract to the page
+*[[Transport inhibitor response 1|Transport inhibitor response 1]]
-(as it appears on PubMed at http://www.pubmed.gov), where 18391211 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_18391211}}
+__TOC__
+</StructureSection>
-==About this Structure==
-C6P is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C6P OCA].
-==Reference==
-<ref group="xtra">PMID:18391211</ref><references group="xtra"/>
 [[Category: Arabidopsis thaliana]]
-[[Category: Tan, X.]]
+[[Category: Large Structures]]
-[[Category: Auxin]]
+[[Category: Tan X]]
-[[Category: Auxin signaling pathway]]
-[[Category: Cell cycle]]
-[[Category: Chemical biology]]
-[[Category: Chromosome partition]]
-[[Category: Cytoplasm]]
-[[Category: Cytoskeleton]]
-[[Category: Developmental protein]]
-[[Category: Ethylene signaling pathway]]
-[[Category: F-box]]
-[[Category: Leucine-rich repeat]]
-[[Category: Nucleus]]
-[[Category: Plant defense]]
-[[Category: Plant physiology]]
-[[Category: Signaling protein]]
-[[Category: Small molecule]]
-[[Category: Ubiquitin ligase]]
-[[Category: Ubl conjugation pathway]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 20:08:52 2009''