Fluorine in PDB 7p5e: Pyrazole Carboxylic Acid Inhibitors of KEAP1:NRF2 Interaction

The structure of Pyrazole Carboxylic Acid Inhibitors of KEAP1:NRF2 Interaction, PDB code: 7p5e was solved by T.G.Davies, A.Cleasby, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	89.69 / 1.87
Space group	P 61
Cell size a, b, c (Å), α, β, γ (°)	103.569, 103.569, 56.069, 90, 90, 120
R / Rfree (%)	16 / 20.3

The structure of Pyrazole Carboxylic Acid Inhibitors of KEAP1:NRF2 Interaction also contains other interesting chemical elements:

Chlorine

(Cl)

1 atom

The binding sites of Fluorine atom in the Pyrazole Carboxylic Acid Inhibitors of KEAP1:NRF2 Interaction (pdb code 7p5e). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the Pyrazole Carboxylic Acid Inhibitors of KEAP1:NRF2 Interaction, PDB code: 7p5e:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the Pyrazole Carboxylic Acid Inhibitors of KEAP1:NRF2 Interaction


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Pyrazole Carboxylic Acid Inhibitors of KEAP1:NRF2 Interaction within 5.0Å range: probe atom residue distance (Å) B Occ A:F703 b:18.0 occ:0.93 F27 A:5VX703 0.0 18.0 0.9 C26 A:5VX703 1.3 18.5 0.9 F29 A:5VX703 2.1 23.2 0.9 F28 A:5VX703 2.1 18.2 0.9 C25 A:5VX703 2.3 16.1 0.9 N18 A:5VX703 2.8 14.2 0.9 C16 A:5VX703 2.9 14.4 0.9 N17 A:5VX703 2.9 13.6 0.9 H39 A:5VX703 3.4 19.3 0.9 O A:HOH879 3.5 40.9 1.0 CB A:ALA556 3.5 16.0 1.0 N A:ALA556 3.5 15.3 1.0 C21 A:5VX703 3.6 15.9 0.9 C15 A:5VX703 3.7 13.4 0.9 C12 A:5VX703 3.7 14.8 0.9 CB A:SER555 3.8 18.6 1.0 CA A:GLY509 3.9 15.0 1.0 CA A:ALA556 3.9 14.7 1.0 OG A:SER555 4.0 19.5 1.0 H42 A:5VX703 4.1 13.9 0.9 N19 A:5VX703 4.1 13.4 0.9 C A:SER555 4.2 16.2 1.0 C11 A:5VX703 4.2 19.4 0.9 O A:SER508 4.3 17.6 1.0 O A:GLY509 4.4 15.7 1.0 C14 A:5VX703 4.4 13.2 0.9 C13 A:5VX703 4.4 14.4 0.9 C20 A:5VX703 4.5 15.7 0.9 C10 A:5VX703 4.5 17.7 0.9 C22 A:5VX703 4.5 18.4 0.9 O24 A:5VX703 4.5 24.1 0.9 O A:HOH941 4.5 21.8 1.0 CA A:SER555 4.6 17.4 1.0 O A:DMS701 4.6 41.6 1.0 C A:GLY509 4.6 15.5 1.0 N A:GLY509 4.7 14.8 1.0 C1 A:DMS701 4.7 47.8 1.0 C A:SER508 4.8 15.9 1.0 O A:SER555 4.9 17.1 1.0 O A:HOH983 4.9 30.4 1.0

Fluorine binding site 2 out of 3 in the Pyrazole Carboxylic Acid Inhibitors of KEAP1:NRF2 Interaction


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Pyrazole Carboxylic Acid Inhibitors of KEAP1:NRF2 Interaction within 5.0Å range: probe atom residue distance (Å) B Occ A:F703 b:18.2 occ:0.93 F28 A:5VX703 0.0 18.2 0.9 C26 A:5VX703 1.3 18.5 0.9 F27 A:5VX703 2.1 18.0 0.9 F29 A:5VX703 2.1 23.2 0.9 C25 A:5VX703 2.4 16.1 0.9 O A:HOH983 3.0 30.4 1.0 C1 A:DMS701 3.0 47.8 1.0 H39 A:5VX703 3.0 19.3 0.9 O A:HOH941 3.1 21.8 1.0 N17 A:5VX703 3.1 13.6 0.9 N18 A:5VX703 3.2 14.2 0.9 O A:HOH879 3.3 40.9 1.0 C21 A:5VX703 3.4 15.9 0.9 C16 A:5VX703 3.6 14.4 0.9 O24 A:5VX703 3.6 24.1 0.9 C2 A:DMS701 3.7 48.9 1.0 C11 A:5VX703 3.7 19.4 0.9 S A:DMS701 3.9 56.2 1.0 O A:DMS701 3.9 41.6 1.0 C22 A:5VX703 4.0 18.4 0.9 C12 A:5VX703 4.1 14.8 0.9 C10 A:5VX703 4.3 17.7 0.9 N19 A:5VX703 4.4 13.4 0.9 C20 A:5VX703 4.4 15.7 0.9 OG A:SER555 4.6 19.5 1.0 C6 A:5VX703 4.7 20.9 0.9 H35 A:5VX703 4.7 34.1 0.9 C4 A:5VX703 4.8 22.3 0.9 CB A:ALA556 4.8 16.0 1.0 C15 A:5VX703 4.8 13.4 0.9 H33 A:5VX703 4.9 33.7 0.9 N2 A:5VX703 4.9 31.3 0.9 CB A:SER555 5.0 18.6 1.0

Fluorine binding site 3 out of 3 in the Pyrazole Carboxylic Acid Inhibitors of KEAP1:NRF2 Interaction


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Pyrazole Carboxylic Acid Inhibitors of KEAP1:NRF2 Interaction within 5.0Å range: probe atom residue distance (Å) B Occ A:F703 b:23.2 occ:0.93 F29 A:5VX703 0.0 23.2 0.9 C26 A:5VX703 1.3 18.5 0.9 F27 A:5VX703 2.1 18.0 0.9 F28 A:5VX703 2.1 18.2 0.9 C25 A:5VX703 2.4 16.1 0.9 O24 A:5VX703 2.8 24.1 0.9 C21 A:5VX703 3.0 15.9 0.9 C22 A:5VX703 3.1 18.4 0.9 C2 A:DMS701 3.3 48.9 1.0 CB A:TYR525 3.4 24.2 1.0 O A:DMS701 3.5 41.6 1.0 N18 A:5VX703 3.6 14.2 0.9 CB A:SER555 3.9 18.6 1.0 O A:SER508 3.9 17.6 1.0 OG A:SER555 3.9 19.5 1.0 O A:HOH983 4.0 30.4 1.0 S A:DMS701 4.0 56.2 1.0 C1 A:DMS701 4.0 47.8 1.0 O A:HOH879 4.1 40.9 1.0 CG A:TYR525 4.1 27.1 1.0 O23 A:5VX703 4.1 17.6 0.9 C20 A:5VX703 4.3 15.7 0.9 C16 A:5VX703 4.3 14.4 0.9 CD2 A:TYR525 4.4 30.5 1.0 N17 A:5VX703 4.5 13.6 0.9 N19 A:5VX703 4.6 13.4 0.9 C A:SER508 4.6 15.9 1.0 CA A:TYR525 4.7 23.9 1.0 CA A:GLY509 4.7 15.0 1.0 N A:TYR525 4.7 21.1 1.0 H39 A:5VX703 4.8 19.3 0.9 O A:HOH941 4.9 21.8 1.0 CD1 A:TYR525 4.9 29.4 1.0 N A:GLY509 5.0 14.8 1.0

D.Norton, W.G.Bonnette, J.F.Callahan, M.G.Carr, C.M.Griffiths-Jones, T.D.Heightman, J.K.Kerns, H.Nie, S.J.Rich, C.Richardson, W.Rumsey, Y.Sanchez, M.L.Verdonk, H.M.G.Willems, W.E.Wixted, L.Wolfe 3Rd, A.J.Woolford, Z.Wu, T.G.Davies. Fragment-Guided Discovery of Pyrazole Carboxylic Acid Inhibitors of the Kelch-Like Ech-Associated Protein 1: Nuclear Factor Erythroid 2 Related Factor 2 (KEAP1:NRF2) Protein-Protein Interaction. J.Med.Chem. 2021.
ISSN: ISSN 0022-2623
PubMed: 34705450
DOI: 10.1021/ACS.JMEDCHEM.1C01351