Fluorine in PDB 7p58: Pyrazole Carboxylic Acid Inhibitors of KEAP1:NRF2 Interaction

The structure of Pyrazole Carboxylic Acid Inhibitors of KEAP1:NRF2 Interaction, PDB code: 7p58 was solved by T.G.Davies, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	90.06 / 1.89
Space group	P 61
Cell size a, b, c (Å), α, β, γ (°)	103.996, 103.996, 55.965, 90, 90, 120
R / Rfree (%)	18.1 / 22.6

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 7p58). 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: 7p58:
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:26.1 occ:0.95 F26 A:5UI703 0.0 26.1 0.9 C25 A:5UI703 1.3 25.1 0.9 F27 A:5UI703 2.1 20.5 0.9 F28 A:5UI703 2.1 23.4 0.9 C24 A:5UI703 2.4 20.7 0.9 O22 A:5UI703 2.7 25.1 0.9 C20 A:5UI703 2.9 18.2 0.9 C21 A:5UI703 3.0 22.6 0.9 C1 A:DMS701 3.4 30.6 1.0 CB A:TYR525 3.5 29.0 1.0 S A:DMS701 3.5 31.9 1.0 N17 A:5UI703 3.6 18.4 0.9 O A:DMS701 3.7 33.7 1.0 CB A:SER555 3.8 23.5 1.0 O A:SER508 3.9 20.0 1.0 O A:HOH946 3.9 24.8 1.0 OG A:SER555 4.0 24.1 1.0 O23 A:5UI703 4.1 21.6 0.9 CG A:TYR525 4.1 32.0 1.0 C19 A:5UI703 4.2 18.6 0.9 C15 A:5UI703 4.4 18.3 0.9 CD2 A:TYR525 4.5 35.5 1.0 N16 A:5UI703 4.5 16.7 0.9 N18 A:5UI703 4.6 16.8 0.9 H30 A:5UI703 4.6 27.7 0.9 C A:SER508 4.7 18.6 1.0 H32 A:5UI703 4.7 28.8 0.9 H39 A:5UI703 4.7 23.4 0.9 CA A:TYR525 4.8 27.4 1.0 O A:HOH877 4.8 27.7 1.0 N A:TYR525 4.8 25.2 1.0 CA A:GLY509 4.8 18.0 1.0 CD1 A:TYR525 4.8 34.6 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:20.5 occ:0.95 F27 A:5UI703 0.0 20.5 0.9 C25 A:5UI703 1.3 25.1 0.9 F26 A:5UI703 2.1 26.1 0.9 F28 A:5UI703 2.2 23.4 0.9 C24 A:5UI703 2.4 20.7 0.9 N17 A:5UI703 2.9 18.4 0.9 C15 A:5UI703 3.0 18.3 0.9 N16 A:5UI703 3.0 16.7 0.9 H39 A:5UI703 3.4 23.4 0.9 CB A:ALA556 3.5 22.5 1.0 N A:ALA556 3.5 19.2 1.0 C20 A:5UI703 3.6 18.2 0.9 H30 A:5UI703 3.6 27.7 0.9 CB A:SER555 3.7 23.5 1.0 C14 A:5UI703 3.8 16.3 0.9 C11 A:5UI703 3.8 16.9 0.9 OG A:SER555 3.9 24.1 1.0 CA A:ALA556 3.9 19.2 1.0 CA A:GLY509 4.0 18.0 1.0 C A:SER555 4.1 20.2 1.0 N18 A:5UI703 4.2 16.8 0.9 H42 A:5UI703 4.2 16.7 0.9 C10 A:5UI703 4.2 22.2 0.9 H32 A:5UI703 4.2 28.8 0.9 O A:SER508 4.3 20.0 1.0 CA A:SER555 4.4 21.8 1.0 O A:GLY509 4.5 19.6 1.0 C21 A:5UI703 4.5 22.6 0.9 C19 A:5UI703 4.5 18.6 0.9 O22 A:5UI703 4.5 25.1 0.9 C13 A:5UI703 4.5 14.9 0.9 C12 A:5UI703 4.5 16.9 0.9 C9 A:5UI703 4.5 22.6 0.9 O A:HOH877 4.6 27.7 1.0 C1 A:5UI703 4.6 27.2 0.9 S A:DMS701 4.6 31.9 1.0 O A:DMS701 4.7 33.7 1.0 C A:GLY509 4.7 18.2 1.0 N A:GLY509 4.8 17.4 1.0 O A:HOH946 4.9 24.8 1.0 O A:SER555 4.9 20.7 1.0 C2 A:5UI703 4.9 29.8 0.9 C A:SER508 4.9 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:23.4 occ:0.95 F28 A:5UI703 0.0 23.4 0.9 C25 A:5UI703 1.3 25.1 0.9 F26 A:5UI703 2.1 26.1 0.9 F27 A:5UI703 2.2 20.5 0.9 C24 A:5UI703 2.4 20.7 0.9 H39 A:5UI703 2.8 23.4 0.9 H32 A:5UI703 2.9 28.8 0.9 O A:HOH946 2.9 24.8 1.0 O A:HOH877 3.1 27.7 1.0 N16 A:5UI703 3.1 16.7 0.9 N17 A:5UI703 3.2 18.4 0.9 C20 A:5UI703 3.4 18.2 0.9 H30 A:5UI703 3.5 27.7 0.9 S A:DMS701 3.5 31.9 1.0 O22 A:5UI703 3.6 25.1 0.9 C15 A:5UI703 3.6 18.3 0.9 C10 A:5UI703 3.7 22.2 0.9 C2 A:5UI703 3.8 29.8 0.9 C1 A:DMS701 3.9 30.6 1.0 C21 A:5UI703 4.0 22.6 0.9 C1 A:5UI703 4.1 27.2 0.9 C11 A:5UI703 4.1 16.9 0.9 O A:DMS701 4.3 33.7 1.0 N18 A:5UI703 4.4 16.8 0.9 C9 A:5UI703 4.4 22.6 0.9 H35 A:5UI703 4.4 32.2 0.9 C19 A:5UI703 4.4 18.6 0.9 C5 A:5UI703 4.6 27.1 0.9 H31 A:5UI703 4.6 27.1 0.9 OG A:SER555 4.7 24.1 1.0 O4 A:5UI703 4.7 25.4 0.9 C3 A:5UI703 4.7 33.3 0.9 H29 A:5UI703 4.8 27.7 0.9 CB A:ALA556 4.9 22.5 1.0 C14 A:5UI703 4.9 16.3 0.9 CB A:SER555 5.0 23.5 1.0 C2 A:DMS701 5.0 39.6 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