View source for 2xpb


==DISCOVERY OF CELL-ACTIVE PHENYL-IMIDAZOLE PIN1 INHIBITORS BY STRUCTURE-GUIDED FRAGMENT EVOLUTION==
<StructureSection load='2xpb' size='340' side='right'caption='[[2xpb]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2xpb]] 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=2XPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XPB FirstGlance]. <br>
</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&#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=4GE:5-[BENZYL(METHYL)CARBAMOYL]-2-(3-CHLOROPHENYL)-1H-IMIDAZOLE-4-CARBOXYLIC+ACID'>4GE</scene></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=2xpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xpb OCA], [https://pdbe.org/2xpb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xpb RCSB], [https://www.ebi.ac.uk/pdbsum/2xpb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xpb 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pin1 is an emerging oncology target strongly implicated in Ras and ErbB2-mediated tumourigenesis. Pin1 isomerizes bonds linking phospho-serine/threonine moieties to proline enabling it to play a key role in proline-directed kinase signalling. Here we report a novel series of Pin1 inhibitors based on a phenyl imidazole acid core that contains sub-muM inhibitors. Compounds have been identified that block prostate cancer cell growth under conditions where Pin1 is essential.

Discovery of cell-active phenyl-imidazole Pin1 inhibitors by structure-guided fragment evolution.,Potter A, Oldfield V, Nunns C, Fromont C, Ray S, Northfield CJ, Bryant CJ, Scrace SF, Robinson D, Matossova N, Baker L, Dokurno P, Surgenor AE, Davis B, Richardson CM, Murray JB, Moore JD Bioorg Med Chem Lett. 2010 Nov 15;20(22):6483-8. Epub 2010 Sep 17. PMID:20932746<ref>PMID:20932746</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2xpb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Peptidyl-prolyl cis-trans isomerase 3D structures|Peptidyl-prolyl cis-trans isomerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Baker L]]
[[Category: Bryant CJ]]
[[Category: Davis BE]]
[[Category: Dokurno P]]
[[Category: Fromont C]]
[[Category: Matossova N]]
[[Category: Moore JD]]
[[Category: Murray JB]]
[[Category: Northfield CJ]]
[[Category: Nunns C]]
[[Category: Oldfield V]]
[[Category: Potter A]]
[[Category: Ray S]]
[[Category: Richardson CM]]
[[Category: Robinson D]]
[[Category: Scrace SF]]
[[Category: Surgenor AE]]