6p5v

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'''Unreleased structure'''
 
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The entry 6p5v is ON HOLD
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==Structure of DCN1 bound to N-((4S,5S)-7-ethyl-4-(4-fluorophenyl)-3-methyl-6-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-methylbenzamide==
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<StructureSection load='6p5v' size='340' side='right'caption='[[6p5v]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6p5v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P5V 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]] 1.398&#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=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=O37:N-[(4S,5S)-1-[(1S)-cyclohex-3-en-1-yl]-7-ethyl-4-(4-fluorophenyl)-3-methyl-6-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridin-5-yl]-3-methylbenzamide'>O37</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=6p5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p5v OCA], [https://pdbe.org/6p5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p5v RCSB], [https://www.ebi.ac.uk/pdbsum/6p5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p5v ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/D9IEF7_BPT4 D9IEF7_BPT4] [https://www.uniprot.org/uniprot/DCNL1_HUMAN DCNL1_HUMAN] Part of an E3 ubiquitin ligase complex for neddylation. Required for neddylation of cullin components of E3 cullin-RING ubiquitin ligase complexes by enhancing the rate of cullins neddylation. Functions to recruit the NEDD8-charged E2 enzyme to the cullin component. Involved in the release of inhibitory effets of CAND1 on cullin-RING ligase E3 complex assembly and activity. Acts also as an oncogene facilitating malignant transformation and carcinogenic progression (By similarity).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Chemical control of cullin neddylation is attracting increased attention based largely on the successes of the NEDD8-activating enzyme (E1) inhibitor pevonedistat. Recently reported chemical probes enable selective and time-dependent inhibition of downstream members of the neddylation trienzymatic cascade including the co-E3, DCN1. In this work, we report the optimization of a novel class of small molecule inhibitors of the DCN1-UBE2M interaction. Rational X-ray co-structure enabled optimization afforded a 25-fold improvement in potency relative to the initial screening hit. The potency gains are largely attributed to additional hydrophobic interactions mimicking the N-terminal acetyl group that drives binding of UBE2M to DCN1. The compounds inhibit the protein-protein interaction, block NEDD8 transfer in biochemical assays, engage DCN1 in cells, and selectively reduce the steady-state neddylation of Cul1 and Cul3 in two squamous carcinoma cell lines harboring DCN1 amplification.
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Authors: Guy, R.K., Kim, H.S., Hammill, J.T., Scott, D.C., Schulman, B.A.
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Discovery of Novel Pyrazolo-pyridone DCN1 Inhibitors Controlling Cullin Neddylation.,Kim HS, Hammill JT, Scott DC, Chen Y, Min J, Rector J, Singh B, Schulman BA, Guy RK J Med Chem. 2019 Sep 26;62(18):8429-8442. doi: 10.1021/acs.jmedchem.9b00410. Epub, 2019 Sep 13. PMID:31465221<ref>PMID:31465221</ref>
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Description: Structure of DCN1 bound to N-((4S,5S)-7-ethyl-4-(4-fluorophenyl)-3-methyl-6-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-methylbenzamide
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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: Scott, D.C]]
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<div class="pdbe-citations 6p5v" style="background-color:#fffaf0;"></div>
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[[Category: Guy, R.K]]
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== References ==
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[[Category: Kim, H.S]]
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<references/>
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[[Category: Hammill, J.T]]
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__TOC__
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[[Category: Schulman, B.A]]
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</StructureSection>
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[[Category: Escherichia virus T4]]
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Guy RK]]
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[[Category: Hammill JT]]
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[[Category: Kim HS]]
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[[Category: Schulman BA]]
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[[Category: Scott DC]]

Current revision

Structure of DCN1 bound to N-((4S,5S)-7-ethyl-4-(4-fluorophenyl)-3-methyl-6-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-methylbenzamide

PDB ID 6p5v

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