3i6c
From Proteopedia
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<StructureSection load='3i6c' size='340' side='right'caption='[[3i6c]], [[Resolution|resolution]] 1.30Å' scene=''> | <StructureSection load='3i6c' size='340' side='right'caption='[[3i6c]], [[Resolution|resolution]] 1.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3i6c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[3i6c]] is a 2 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=3I6C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I6C FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.3Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GIA:3-FLUORO-N-(NAPHTHALEN-2-YLCARBONYL)-D-PHENYLALANINE'>GIA</scene></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=3i6c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i6c OCA], [https://pdbe.org/3i6c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i6c RCSB], [https://www.ebi.ac.uk/pdbsum/3i6c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i6c ProSAT]</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=3i6c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i6c OCA], [https://pdbe.org/3i6c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i6c RCSB], [https://www.ebi.ac.uk/pdbsum/3i6c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i6c ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</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=3i6c ConSurf]. | </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=3i6c ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Following the discovery of a novel series of phosphate-containing small molecular Pin1 inhibitors, the drug design strategy shifted to replacement of the phosphate group with an isostere with potential better pharmaceutical properties. The initial loss in potency of carboxylate analogs was likely due to weaker charge-charge interactions in the putative phosphate binding pocket and was subsequently recovered by structure-based optimization of ligand-protein interactions in the proline binding site, leading to the discovery of a sub-micromolar non-phosphate small molecular Pin1 inhibitor. | ||
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| - | Structure-based design of novel human Pin1 inhibitors (II).,Dong L, Marakovits J, Hou X, Guo C, Greasley S, Dagostino E, Ferre R, Johnson MC, Kraynov E, Thomson J, Pathak V, Murray BW Bioorg Med Chem Lett. 2010 Apr 1;20(7):2210-4. Epub 2010 Feb 14. PMID:20207139<ref>PMID:20207139</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 3i6c" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | + | [[Category: Ferre RA]] | |
| - | [[Category: Ferre | + | [[Category: Greasley SE]] |
| - | [[Category: Greasley | + | |
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Current revision
Structure-Based Design of Novel PIN1 Inhibitors (II)
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