6dcy: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6dcy is ON HOLD  until Paper Publication
+==The N-terminal domain of PA endonuclease from the influenza H1N1 virus in complex with 5-hydroxy-2-methyl-4-oxo-4H-pyran-3-carboxylic acid==
+<StructureSection load='6dcy' size='340' side='right'caption='[[6dcy]], [[Resolution|resolution]] 2.08&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6dcy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/California/04/2009(H1N1)) Influenza A virus (A/California/04/2009(H1N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DCY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DCY FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.08&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G5V:5-hydroxy-2-methyl-4-oxo-4H-pyran-3-carboxylic+acid'>G5V</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></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=6dcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dcy OCA], [https://pdbe.org/6dcy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dcy RCSB], [https://www.ebi.ac.uk/pdbsum/6dcy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dcy ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/C3W5S0_I09A0 C3W5S0_I09A0]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Metalloenzymes represent an important target space for drug discovery. A limitation to the early development of metalloenzyme inhibitors has been the lack of established structure-activity relationships (SARs) for molecules that bind the metal ion cofactor(s) of a metalloenzyme. Herein, we employed a bioinorganic perspective to develop an SAR for inhibition of the metalloenzyme influenza RNA polymerase PAN endonuclease. The identified trends highlight the importance of the electronics of the metal-binding pharmacophore (MBP), in addition to MBP sterics, for achieving improved inhibition and selectivity. By optimization of the MBPs for PAN endonuclease, a class of highly active and selective fragments was developed that displays IC50 values &lt;50 nM. This SAR led to structurally distinct molecules that also displayed IC50 values of approximately 10 nM, illustrating the utility of a metal-centric development campaign in generating highly active and selective metalloenzyme inhibitors.
-Authors:
+Structure-Activity Relationships in Metal-Binding Pharmacophores for Influenza Endonuclease.,Credille CV, Dick BL, Morrison CN, Stokes RW, Adamek RN, Wu NC, Wilson IA, Cohen SM J Med Chem. 2018 Oct 31. doi: 10.1021/acs.jmedchem.8b01363. PMID:30351002<ref>PMID:30351002</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6dcy" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Cohen SM]]
+[[Category: Dick BL]]
+[[Category: Morrison CN]]