1k5r: Difference between revisions

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-{{Seed}}
-[[Image:1k5r.png|left|200px]]
-<!--
+==YAP65 WW domain S24-Amino-Ethylsulfanyl-Acetic Acid mutant==
-The line below this paragraph, containing "STRUCTURE_1k5r", creates the "Structure Box" on the page.
+<StructureSection load='1k5r' size='340' side='right'caption='[[1k5r]]' 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'>[[1k5r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K5R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1K5R 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">Solution NMR, 10 models</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ESD:(2-AMINO-ETHYLSULFANYL)-ACETIC+ACID'>ESD</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
-{{STRUCTURE_1k5r|  PDB=1k5r  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1k5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k5r OCA], [https://pdbe.org/1k5r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1k5r RCSB], [https://www.ebi.ac.uk/pdbsum/1k5r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1k5r ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/YAP1_HUMAN YAP1_HUMAN] Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Plays a key role to control cell proliferation in response to cell contact. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage-independent growth, and epithelial mesenchymal transition (EMT) induction. Isoform 2 and isoform 3 can activate the C-terminal fragment (CTF) of ERBB4 (isoform 3).<ref>PMID:12807903</ref> <ref>PMID:17974916</ref> <ref>PMID:18579750</ref> <ref>PMID:18158288</ref> <ref>PMID:18280240</ref> <ref>PMID:21364637</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/k5/1k5r_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1k5r ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Chemical synthesis allows the incorporation of nonnatural amino acids into proteins that may provide previously untried probes of their folding pathway and thermodynamic stability. We have used a flexible thioether linker as a loop mimetic in the human yes kinase-associated protein (YAP 65) WW domain, a three-stranded, 44-residue, beta-sheet protein. This linkage avoids problems of incorporating sequences that constrain loops to the extent that they significantly change the nature of the denatured state with concomitant effects on the folding kinetics. An NMR solution structure shows that the thioether linker had little effect on the global fold of the domain, although the loop is apparently more dynamic. The thioether variants are destabilized by up to 1.4 kcal/mol (1 cal = 4.18 J). Preliminary Phi-value analysis showed that the first loop is highly structured in the folding transition state, and the second loop is essentially unstructured. These data are consistent with results from simulated unfolding and detailed protein-engineering studies of structurally homologous WW domains. Previously, Phi-value analysis was limited to studying side-chain interactions. The linkers used here extend the protein engineering method directly to secondary-structure interactions.
-===YAP65 WW domain S24-Amino-Ethylsulfanyl-Acetic Acid mutant===
+Using flexible loop mimetics to extend phi-value analysis to secondary structure interactions.,Ferguson N, Pires JR, Toepert F, Johnson CM, Pan YP, Volkmer-Engert R, Schneider-Mergener J, Daggett V, Oschkinat H, Fersht A Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13008-13. Epub 2001 Oct 30. PMID:11687614<ref>PMID:11687614</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<!--
+</div>
-The line below this paragraph, {{ABSTRACT_PUBMED_11687614}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 1k5r" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 11687614 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_11687614}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Homo sapiens]]
-K5R is a [[Single protein]] structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K5R OCA].
+[[Category: Large Structures]]
+[[Category: Daggett V]]
-==Reference==
+[[Category: Ferguson N]]
-Using flexible loop mimetics to extend phi-value analysis to secondary structure interactions., Ferguson N, Pires JR, Toepert F, Johnson CM, Pan YP, Volkmer-Engert R, Schneider-Mergener J, Daggett V, Oschkinat H, Fersht A, Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13008-13. Epub 2001 Oct 30. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11687614 11687614]
+[[Category: Fersht AR]]
-[[Category: Single protein]]
+[[Category: Johnson CM]]
-[[Category: Daggett, V.]]
+[[Category: Oschkinat H]]
-[[Category: Ferguson, N.]]
+[[Category: Pan YP]]
-[[Category: Fersht, A R.]]
+[[Category: Pires JR]]
-[[Category: Johnson, C M.]]
+[[Category: Schneider-Mergener J]]
-[[Category: Oschkinat, H.]]
+[[Category: Toepert F]]
-[[Category: Pan, Y P.]]
+[[Category: Volkmer-Engert R]]
-[[Category: Pires, J R.]]
-[[Category: Schneider-Mergener, J.]]
-[[Category: Toepert, F.]]
-[[Category: Volkmer-Engert, R.]]
-[[Category: Beta-sheet protein]]
-[[Category: Stability of beta sheet]]
-[[Category: Ww domain]]
-[[Category: Yap65]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul  2 09:49:54 2008''