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==DISCOVERY OF CELL-ACTIVE PHENYL-IMIDAZOLE PIN1 INHIBITORS BY STRUCTURE-GUIDED FRAGMENT EVOLUTION==
==DISCOVERY OF CELL-ACTIVE PHENYL-IMIDAZOLE PIN1 INHIBITORS BY STRUCTURE-GUIDED FRAGMENT EVOLUTION==
<StructureSection load='2xp8' size='340' side='right' caption='[[2xp8]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
<StructureSection load='2xp8' size='340' side='right'caption='[[2xp8]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2xp8]] is a 1 chain structure with 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=2XP8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XP8 FirstGlance]. <br>
<table><tr><td colspan='2'>[[2xp8]] 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=2XP8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XP8 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=12P:DODECAETHYLENE+GLYCOL'>12P</scene>, <scene name='pdbligand=4FY:4-(MORPHOLIN-4-YLCARBONYL)-2-PHENYL-1H-IMIDAZOLE-5-CARBOXYLIC+ACID'>4FY</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]] 2.1&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1f8a|1f8a]], [[1i8g|1i8g]], [[1pin|1pin]], [[2xpb|2xpb]], [[2xp3|2xp3]], [[2xp5|2xp5]], [[1nmw|1nmw]], [[1zcn|1zcn]], [[2xp4|2xp4]], [[2f21|2f21]], [[2xp6|2xp6]], [[1nmv|1nmv]], [[2xp9|2xp9]], [[2xp7|2xp7]], [[1i8h|1i8h]], [[2xpa|2xpa]], [[1i6c|1i6c]]</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=4FY:4-(MORPHOLIN-4-YLCARBONYL)-2-PHENYL-1H-IMIDAZOLE-5-CARBOXYLIC+ACID'>4FY</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </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=2xp8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xp8 OCA], [https://pdbe.org/2xp8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xp8 RCSB], [https://www.ebi.ac.uk/pdbsum/2xp8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xp8 ProSAT]</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=2xp8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xp8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xp8 RCSB], [http://www.ebi.ac.uk/pdbsum/2xp8 PDBsum]</span></td></tr>
</table>
</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>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 2xp8" style="background-color:#fffaf0;"></div>
==See Also==
*[[Peptidyl-prolyl cis-trans isomerase 3D structures|Peptidyl-prolyl cis-trans isomerase 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Peptidylprolyl isomerase]]
[[Category: Large Structures]]
[[Category: Baker, L.]]
[[Category: Baker L]]
[[Category: Bryant, C J.]]
[[Category: Bryant CJ]]
[[Category: Davis, B E.]]
[[Category: Davis BE]]
[[Category: Dokurno, P.]]
[[Category: Dokurno P]]
[[Category: Fromont, C.]]
[[Category: Fromont C]]
[[Category: Matossova, N.]]
[[Category: Matossova N]]
[[Category: Moore, J D.]]
[[Category: Moore JD]]
[[Category: Murray, J B.]]
[[Category: Murray JB]]
[[Category: Northfield, C J.]]
[[Category: Northfield CJ]]
[[Category: Nunns, C.]]
[[Category: Nunns C]]
[[Category: Oldfield, V.]]
[[Category: Oldfield V]]
[[Category: Potter, A.]]
[[Category: Potter A]]
[[Category: Ray, S.]]
[[Category: Ray S]]
[[Category: Richardson, C M.]]
[[Category: Richardson CM]]
[[Category: Robinson, D.]]
[[Category: Robinson D]]
[[Category: Scrace, S F.]]
[[Category: Scrace SF]]
[[Category: Surgenor, A E.]]
[[Category: Surgenor AE]]
[[Category: Cell cycle]]
[[Category: Isomerase]]
[[Category: Oncogenic transformation]]
[[Category: Proline directed kinase]]

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