3kai: Difference between revisions

← Older edit

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

OCA

@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:3kai.png|left|200px]]
-<!--
+==Structure-guided design of alpha-amino acid-derived Pin1 inhibitors==
-The line below this paragraph, containing "STRUCTURE_3kai", creates the "Structure Box" on the page.
+<StructureSection load='3kai' size='340' side='right'caption='[[3kai]], [[Resolution|resolution]] 1.90&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'>[[3kai]] 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=3KAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KAI 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]] 1.9&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=12P:DODECAETHYLENE+GLYCOL'>12P</scene>, <scene name='pdbligand=4FI:(2R)-2-[(2-METHYL-5-PHENYL-PYRAZOL-3-YL)CARBONYLAMINO]-3-NAPHTHALEN-2-YL-PROPANOIC+ACID'>4FI</scene></td></tr>
-{{STRUCTURE_3kai|  PDB=3kai  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3kai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kai OCA], [https://pdbe.org/3kai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kai RCSB], [https://www.ebi.ac.uk/pdbsum/3kai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kai ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PIN1_HUMAN PIN1_HUMAN] Essential PPIase that regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Displays a preference for an acidic residue N-terminal to the isomerized proline bond. Catalyzes pSer/Thr-Pro cis/trans isomerizations. Down-regulates kinase activity of BTK. Can transactivate multiple oncogenes and induce centrosome amplification, chromosome instability and cell transformation. Required for the efficient dephosphorylation and recycling of RAF1 after mitogen activation.<ref>PMID:15664191</ref> <ref>PMID:16644721</ref> <ref>PMID:21497122</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/ka/3kai_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=3kai ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The peptidyl prolyl cis/trans isomerase Pin1 is a promising molecular target for anti-cancer therapeutics. Here we report the structure-guided evolution of an indole 2-carboxylic acid fragment hit into a series of alpha-benzimidazolyl-substituted amino acids. Examples inhibited Pin1 activity with IC(50) &lt;100nM, but were inactive on cells. Replacement of the benzimidazole ring with a naphthyl group resulted in a 10-50-fold loss in ligand potency, but these examples downregulated biomarkers of Pin1 activity and blocked proliferation of PC3 cells.
-===Structure-guided design of alpha-amino acid-derived Pin1 inhibitors===
+Structure-guided design of alpha-amino acid-derived Pin1 inhibitors.,Potter AJ, Ray S, Gueritz L, Nunns CL, Bryant CJ, Scrace SF, Matassova N, Baker L, Dokurno P, Robinson DA, Surgenor AE, Davis B, Murray JB, Richardson CM, Moore JD Bioorg Med Chem Lett. 2010 Jan 15;20(2):586-90. Epub 2009 Nov 22. PMID:19969456<ref>PMID:19969456</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3kai" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_19969456}}, adds the Publication Abstract to the page
+*[[Peptidyl-prolyl cis-trans isomerase 3D structures|Peptidyl-prolyl cis-trans isomerase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 19969456 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_19969456}}
+__TOC__
+</StructureSection>
-==About this Structure==
-KAI is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KAI OCA].
-==Reference==
-<ref group="xtra">PMID:19969456</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Peptidylprolyl isomerase]]
+[[Category: Large Structures]]
-[[Category: Baker, L M.]]
+[[Category: Baker LM]]
-[[Category: Dokurno, P.]]
+[[Category: Dokurno P]]
-[[Category: Moore, J D.]]
+[[Category: Moore JD]]
-[[Category: Murray, J B.]]
+[[Category: Murray JB]]
-[[Category: Potter, A J.]]
+[[Category: Potter AJ]]
-[[Category: Robinson, D A.]]
+[[Category: Robinson DA]]
-[[Category: Surgenor, A E.]]
+[[Category: Surgenor AE]]
-[[Category: Cell cycle]]
-[[Category: Isomerase]]
-[[Category: Nucleus]]
-[[Category: Oncogenic transformation]]
-[[Category: Phosphoprotein]]
-[[Category: Ppiase]]
-[[Category: Proline directed kinase]]
-[[Category: Rotamase]]
-[[Category: Sbdd]]
-[[Category: Small molecule]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan  6 09:04:55 2010''