3odk

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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==
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<StructureSection load='3odk' size='340' side='right' caption='[[3odk]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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<StructureSection load='3odk' size='340' side='right'caption='[[3odk]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3odk]] 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=3ODK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ODK FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3odk]] 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=3ODK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ODK FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ODK:3-PYRIDIN-2-YL-1H-PYRAZOLE-5-CARBOXYLIC+ACID'>ODK</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kab|3kab]], [[3kac|3kac]], [[3kad|3kad]], [[3kaf|3kaf]], [[3kag|3kag]], [[3kah|3kah]], [[3kai|3kai]], [[3kce|3kce]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ODK:3-PYRIDIN-2-YL-1H-PYRAZOLE-5-CARBOXYLIC+ACID'>ODK</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PIN1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3odk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3odk OCA], [https://pdbe.org/3odk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3odk RCSB], [https://www.ebi.ac.uk/pdbsum/3odk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3odk ProSAT]</span></td></tr>
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<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>
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<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=3odk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3odk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3odk RCSB], [http://www.ebi.ac.uk/pdbsum/3odk PDBsum]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://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>
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
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</div>
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*[[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]]
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[[Category: Peptidylprolyl isomerase]]
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[[Category: Large Structures]]
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[[Category: Baker, L]]
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[[Category: Baker L]]
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[[Category: Bryant, C J]]
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[[Category: Bryant CJ]]
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[[Category: Davis, B E]]
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[[Category: Davis BE]]
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[[Category: Dokurno, P]]
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[[Category: Dokurno P]]
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[[Category: Fromont, C]]
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[[Category: Fromont C]]
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[[Category: Matossova, N]]
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[[Category: Matossova N]]
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[[Category: Moore, J D]]
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[[Category: Moore JD]]
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[[Category: Murray, J B]]
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[[Category: Murray JB]]
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[[Category: Northfield, C J]]
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[[Category: Northfield CJ]]
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[[Category: Nunns, C]]
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[[Category: Nunns C]]
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[[Category: Oldfield, V]]
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[[Category: Oldfield V]]
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[[Category: Potter, A]]
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[[Category: Potter A]]
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[[Category: Ray, S]]
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[[Category: Ray S]]
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[[Category: Richardson, C M]]
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[[Category: Richardson CM]]
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[[Category: Robinson, D]]
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[[Category: Robinson D]]
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[[Category: Scrace, S F]]
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[[Category: Scrace SF]]
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[[Category: Surgenor, A E]]
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[[Category: Surgenor AE]]
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[[Category: Cell cycle]]
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[[Category: Isomerase]]
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[[Category: Nucleus]]
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[[Category: Oncogenic transformation]]
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[[Category: Phosphoprotein]]
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[[Category: Ppiase]]
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[[Category: Proline directed kinase]]
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[[Category: Rotamase]]
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[[Category: Sbdd]]
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[[Category: Small molecule]]
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Current revision

Discovery of cell-active phenyl-imidazole Pin1 inhibitors by structure-guided fragment evolution

PDB ID 3odk

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