6dcz: Difference between revisions

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'''Unreleased structure'''


The entry 6dcz is ON HOLD  until Paper Publication
==The N-terminal domain of PA endonuclease from the influenza H1N1 virus in complex with 3-hydroxy-4-oxo-4H-pyran-2-carboxylic acid==
<StructureSection load='6dcz' size='340' side='right' caption='[[6dcz]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6dcz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DCZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DCZ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=G5Y:3-hydroxy-4-oxo-4H-pyran-2-carboxylic+acid'>G5Y</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6dcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dcz OCA], [http://pdbe.org/6dcz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dcz RCSB], [http://www.ebi.ac.uk/pdbsum/6dcz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dcz ProSAT]</span></td></tr>
</table>
<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: Dick, B.L., Morrison, C.N., Cohen, S.M.
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: The N-terminal domain of PA endonuclease from the influenza H1N1 virus in complex with 3-hydroxy-4-oxo-4H-pyran-2-carboxylic acid
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Morrison, C.N]]
<div class="pdbe-citations 6dcz" style="background-color:#fffaf0;"></div>
[[Category: Dick, B.L]]
== References ==
[[Category: Cohen, S.M]]
<references/>
__TOC__
</StructureSection>
[[Category: Cohen, S M]]
[[Category: Dick, B L]]
[[Category: Morrison, C N]]
[[Category: Endonuclease]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Influenza]]
[[Category: Inhibitor]]
[[Category: Pa domain]]
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