7efx

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(New page: '''Unreleased structure''' The entry 7efx is ON HOLD Authors: Liping, L., Jiacheng, L., Rui, Z., Yuan, P. Description: Crystal Structure of human PIN1 complexed with covalent inhibitor...)
Current revision (16:53, 29 November 2023) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 7efx is ON HOLD
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==Crystal Structure of human PIN1 complexed with covalent inhibitor==
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<StructureSection load='7efx' size='340' side='right'caption='[[7efx]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[7efx]] 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=7EFX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EFX FirstGlance]. <br>
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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]] 2.41&#8491;</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=J3X:4-((5-bromofuran-2-yl)methyl)-8-(2-chloroacetyl)-1-thia-4,8-diazaspiro[4.5]decan-3-one'>J3X</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=7efx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7efx OCA], [https://pdbe.org/7efx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7efx RCSB], [https://www.ebi.ac.uk/pdbsum/7efx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7efx ProSAT]</span></td></tr>
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</table>
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== Function ==
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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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The unique proline isomerase peptidyl-prolyl isomerase NIMA-interacting-1 (Pin1) is reported to activate numerous cancer-driving pathways simultaneously, and aberrant Pin1 activation is present in many human cancers. Here, we identified a novel hit compound, ZL-Pin01, that covalently modified Pin1 at Cys113 with an half-maximal inhibitory concentration (IC50) of 1.33 +/- 0.07 muM through screening an in-house library. Crystallographic study drove the process of structure-guided optimization and led to the potent inhibitor ZL-Pin13 with an IC50 of 0.067 +/- 0.03 muM. We obtained four co-crystal structures of Pin1 complexed with inhibitors that elucidated the detailed binding mode of the derivatives with Pin1. Interestingly, the co-crystal of Pin1 with ZL-Pin13 obtained by co-crystallization revealed the conformational change of Gln129 induced by the inhibitor. Furthermore, ZL-Pin13 effectively inhibited the proliferation and downregulated the Pin1 substrates in MDA-MB-231 cells. Collectively, we developed a potent covalent inhibitor of Pin1, ZL-Pin13, which could be an effective probe for studying the functional roles of Pin1.
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Authors: Liping, L., Jiacheng, L., Rui, Z., Yuan, P.
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Computational and Structure-Based Development of High Potent Cell-Active Covalent Inhibitor Targeting the Peptidyl-Prolyl Isomerase NIMA-Interacting-1 (Pin1).,Liu L, Zhu R, Li J, Pei Y, Wang S, Xu P, Wang M, Wen Y, Zhang H, Du D, Ding H, Jiang H, Chen K, Zhou B, Yu L, Luo C J Med Chem. 2022 Feb 10;65(3):2174-2190. doi: 10.1021/acs.jmedchem.1c01686. Epub , 2022 Jan 28. PMID:35089030<ref>PMID:35089030</ref>
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Description: Crystal Structure of human PIN1 complexed with covalent inhibitor
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Jiacheng, L]]
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<div class="pdbe-citations 7efx" style="background-color:#fffaf0;"></div>
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[[Category: Rui, Z]]
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[[Category: Yuan, P]]
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==See Also==
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[[Category: Liping, L]]
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*[[Peptidyl-prolyl cis-trans isomerase 3D structures|Peptidyl-prolyl cis-trans isomerase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Li J]]
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[[Category: Liu L]]
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[[Category: Pei Y]]
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[[Category: Zhu R]]

Current revision

Crystal Structure of human PIN1 complexed with covalent inhibitor

PDB ID 7efx

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