6dcy: Difference between revisions
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<StructureSection load='6dcy' size='340' side='right'caption='[[6dcy]], [[Resolution|resolution]] 2.08Å' scene=''> | <StructureSection load='6dcy' size='340' side='right'caption='[[6dcy]], [[Resolution|resolution]] 2.08Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6dcy]] is a 1 chain structure with sequence from [ | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.08Å</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'>[ | <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> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/C3W5S0_I09A0 C3W5S0_I09A0] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 6dcy" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6dcy" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Cohen | [[Category: Cohen SM]] | ||
[[Category: Dick | [[Category: Dick BL]] | ||
[[Category: Morrison | [[Category: Morrison CN]] | ||
Latest revision as of 09:03, 11 October 2023
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 acidThe 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
Structural highlights
FunctionPublication Abstract from PubMedMetalloenzymes 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 <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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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