Fluorine in PDB 6uf0: Crystal Structure of N-(4-((4-Methoxy-N-(2,2,2-Trifluoroethyl)Phenyl) Sulfonamido)Isoquinolin-1-Yl)-N-((4-Methoxyphenyl)Sulfonyl)Glycine Bound to Human KEAP1 Kelch Domain

The structure of Crystal Structure of N-(4-((4-Methoxy-N-(2,2,2-Trifluoroethyl)Phenyl) Sulfonamido)Isoquinolin-1-Yl)-N-((4-Methoxyphenyl)Sulfonyl)Glycine Bound to Human KEAP1 Kelch Domain, PDB code: 6uf0 was solved by P.R.Lazzara, B.P.David, A.Ankireddy, B.G.Richardson, K.Dye, K.M.Ratia, S.P.Reddy, T.W.Moore, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	19.87 / 1.96
Space group	I 1 2 1
Cell size a, b, c (Å), α, β, γ (°)	105.712, 57.350, 130.425, 90.00, 107.53, 90.00
R / Rfree (%)	17.9 / 22.2

The structure of Crystal Structure of N-(4-((4-Methoxy-N-(2,2,2-Trifluoroethyl)Phenyl) Sulfonamido)Isoquinolin-1-Yl)-N-((4-Methoxyphenyl)Sulfonyl)Glycine Bound to Human KEAP1 Kelch Domain also contains other interesting chemical elements:

Sodium

(Na)

2 atoms

The binding sites of Fluorine atom in the Crystal Structure of N-(4-((4-Methoxy-N-(2,2,2-Trifluoroethyl)Phenyl) Sulfonamido)Isoquinolin-1-Yl)-N-((4-Methoxyphenyl)Sulfonyl)Glycine Bound to Human KEAP1 Kelch Domain (pdb code 6uf0). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the Crystal Structure of N-(4-((4-Methoxy-N-(2,2,2-Trifluoroethyl)Phenyl) Sulfonamido)Isoquinolin-1-Yl)-N-((4-Methoxyphenyl)Sulfonyl)Glycine Bound to Human KEAP1 Kelch Domain, PDB code: 6uf0:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the Crystal Structure of N-(4-((4-Methoxy-N-(2,2,2-Trifluoroethyl)Phenyl) Sulfonamido)Isoquinolin-1-Yl)-N-((4-Methoxyphenyl)Sulfonyl)Glycine Bound to Human KEAP1 Kelch Domain


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Crystal Structure of N-(4-((4-Methoxy-N-(2,2,2-Trifluoroethyl)Phenyl) Sulfonamido)Isoquinolin-1-Yl)-N-((4-Methoxyphenyl)Sulfonyl)Glycine Bound to Human KEAP1 Kelch Domain within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:82.7 occ:1.00 F1 A:Q5V701 0.0 82.7 1.0 C13 A:Q5V701 1.4 63.5 1.0 F3 A:Q5V701 2.2 65.5 1.0 F2 A:Q5V701 2.2 71.7 1.0 C10 A:Q5V701 2.5 58.9 1.0 O B:HOH924 2.7 43.8 1.0 N3 A:Q5V701 3.0 49.4 1.0 NH1 A:ARG483 3.4 41.7 1.0 O6 A:Q5V701 3.9 42.1 1.0 C5 A:Q5V701 3.9 43.7 1.0 S2 A:Q5V701 4.0 50.6 1.0 C1 A:Q5V701 4.1 48.3 1.0 OG A:SER508 4.2 27.1 1.0 C21 A:Q5V701 4.2 49.3 1.0 CZ A:ARG483 4.5 41.3 1.0 C20 A:Q5V701 4.5 47.1 1.0 CB A:PHE478 4.6 28.7 1.0 CB A:SER508 4.7 27.5 1.0 CD1 A:ILE461 4.7 36.8 1.0 NH2 A:ARG483 4.8 42.1 1.0 CG A:PHE478 4.8 34.9 1.0 CD2 A:PHE478 4.8 39.4 1.0

Fluorine binding site 2 out of 3 in the Crystal Structure of N-(4-((4-Methoxy-N-(2,2,2-Trifluoroethyl)Phenyl) Sulfonamido)Isoquinolin-1-Yl)-N-((4-Methoxyphenyl)Sulfonyl)Glycine Bound to Human KEAP1 Kelch Domain


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Crystal Structure of N-(4-((4-Methoxy-N-(2,2,2-Trifluoroethyl)Phenyl) Sulfonamido)Isoquinolin-1-Yl)-N-((4-Methoxyphenyl)Sulfonyl)Glycine Bound to Human KEAP1 Kelch Domain within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:71.7 occ:1.00 F2 A:Q5V701 0.0 71.7 1.0 C13 A:Q5V701 1.3 63.5 1.0 F3 A:Q5V701 2.2 65.5 1.0 F1 A:Q5V701 2.2 82.7 1.0 C10 A:Q5V701 2.2 58.9 1.0 CD1 A:ILE461 3.0 36.8 1.0 N3 A:Q5V701 3.2 49.4 1.0 CD A:ARG415 3.3 35.8 1.0 CG1 A:ILE461 3.3 30.9 1.0 O B:HOH924 3.6 43.8 1.0 C5 A:Q5V701 3.7 43.7 1.0 NE A:ARG415 3.9 42.2 1.0 C1 A:Q5V701 4.2 48.3 1.0 CG A:ARG415 4.3 33.5 1.0 NH1 A:ARG415 4.3 43.0 1.0 CZ A:ARG415 4.3 44.4 1.0 N A:GLY462 4.4 24.1 1.0 C A:ILE461 4.4 24.5 1.0 CB A:ILE461 4.5 28.7 1.0 C4 A:Q5V701 4.5 39.0 1.0 O A:ILE461 4.5 25.7 1.0 CA A:GLY462 4.6 25.5 1.0 CB A:ARG415 4.6 27.1 1.0 C6 A:Q5V701 4.7 32.5 1.0 CB A:PHE478 4.7 28.7 1.0 S2 A:Q5V701 4.9 50.6 1.0 O A:HOH910 4.9 45.2 1.0 O6 A:Q5V701 5.0 42.1 1.0

Fluorine binding site 3 out of 3 in the Crystal Structure of N-(4-((4-Methoxy-N-(2,2,2-Trifluoroethyl)Phenyl) Sulfonamido)Isoquinolin-1-Yl)-N-((4-Methoxyphenyl)Sulfonyl)Glycine Bound to Human KEAP1 Kelch Domain


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Crystal Structure of N-(4-((4-Methoxy-N-(2,2,2-Trifluoroethyl)Phenyl) Sulfonamido)Isoquinolin-1-Yl)-N-((4-Methoxyphenyl)Sulfonyl)Glycine Bound to Human KEAP1 Kelch Domain within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:65.5 occ:1.00 F3 A:Q5V701 0.0 65.5 1.0 C13 A:Q5V701 1.3 63.5 1.0 F1 A:Q5V701 2.2 82.7 1.0 C10 A:Q5V701 2.2 58.9 1.0 F2 A:Q5V701 2.2 71.7 1.0 CB A:SER508 3.3 27.5 1.0 CB A:PHE478 3.3 28.7 1.0 OG A:SER508 3.5 27.1 1.0 N3 A:Q5V701 3.5 49.4 1.0 NH1 A:ARG483 3.7 41.7 1.0 O A:ILE461 3.7 25.7 1.0 CG1 A:ILE461 3.9 30.9 1.0 O6 A:Q5V701 3.9 42.1 1.0 CG A:PHE478 4.1 34.9 1.0 C A:ILE461 4.2 24.5 1.0 CD1 A:ILE461 4.2 36.8 1.0 N A:PHE478 4.3 27.2 1.0 CA A:GLY462 4.3 25.5 1.0 O B:HOH924 4.4 43.8 1.0 CA A:PHE478 4.4 26.5 1.0 N A:GLY462 4.5 24.1 1.0 S2 A:Q5V701 4.5 50.6 1.0 CD2 A:PHE478 4.5 39.4 1.0 CA A:SER508 4.6 26.7 1.0 C5 A:Q5V701 4.6 43.7 1.0 C A:GLY477 4.7 27.2 1.0 CZ A:ARG483 4.9 41.3 1.0 N A:GLY509 5.0 24.4 1.0 C A:SER508 5.0 24.7 1.0

P.R.Lazzara, B.P.David, A.Ankireddy, B.G.Richardson, K.Dye, K.M.Ratia, S.P.Reddy, T.W.Moore. Isoquinoline Kelch-Like Ech-Associated Protein 1-Nuclear Factor (Erythroid-Derived 2)-Like 2 (KEAP1-NRF2) Inhibitors with High Metabolic Stability. J.Med.Chem. 2019.
ISSN: ISSN 0022-2623
PubMed: 31682434
DOI: 10.1021/ACS.JMEDCHEM.9B01074