6p5v

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 6p5v is ON HOLD until Paper Publication
+
==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==
 +
<StructureSection load='6p5v' size='340' side='right'caption='[[6p5v]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[6p5v]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P5V FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
 +
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DCUN1D1, DCUN1L1, RP42, SCCRO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 +
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span></td></tr>
 +
<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=6p5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p5v OCA], [http://pdbe.org/6p5v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p5v RCSB], [http://www.ebi.ac.uk/pdbsum/6p5v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p5v ProSAT]</span></td></tr>
 +
</table>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
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.
-
Authors: Guy, R.K., Kim, H.S., Hammill, J.T., Scott, D.C., Schulman, B.A.
+
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>
-
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
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
-
[[Category: Scott, D.C]]
+
<div class="pdbe-citations 6p5v" style="background-color:#fffaf0;"></div>
-
[[Category: Guy, R.K]]
+
== References ==
-
[[Category: Kim, H.S]]
+
<references/>
-
[[Category: Hammill, J.T]]
+
__TOC__
-
[[Category: Schulman, B.A]]
+
</StructureSection>
 +
[[Category: Human]]
 +
[[Category: Large Structures]]
 +
[[Category: Lysozyme]]
 +
[[Category: Guy, R K]]
 +
[[Category: Hammill, J T]]
 +
[[Category: Kim, H S]]
 +
[[Category: Schulman, B A]]
 +
[[Category: Scott, D C]]
 +
[[Category: E3 ligase]]
 +
[[Category: Ligase]]

Revision as of 06:15, 10 October 2019

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

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6p5v"
Personal tools