6e0q

The N-terminal domain of PA endonuclease from the influenza H1N1 virus in complex with 4,6-dihydroxy-2-methyl-5-oxocyclohepta-1,3,6-triene-1-carboxylic acid

spinqualitylabelsall models 6e0q, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6e0q is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, HKD, MN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 <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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA