Fluorine in PDB 3ook: Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid

The structure of Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid, PDB code: 3ook was solved by M.G.Rudolph, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	38.14 / 2.29
Space group	C 2 2 21
Cell size a, b, c (Å), α, β, γ (°)	72.477, 83.288, 190.007, 90.00, 90.00, 90.00
R / Rfree (%)	22.9 / 27.1

The structure of Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid also contains other interesting chemical elements:

Chlorine

(Cl)

2 atoms

The binding sites of Fluorine atom in the Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid (pdb code 3ook). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 8 binding sites of Fluorine where determined in the Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid, PDB code: 3ook:
Jump to Fluorine binding site number: 1; 2; 3; 4; 5; 6; 7; 8;

Fluorine binding site 1 out of 8 in the Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid


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 Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid within 5.0Å range: probe atom residue distance (Å) B Occ A:F1 b:36.2 occ:1.00 F26 A:OOK1 0.0 36.2 1.0 C12 A:OOK1 1.3 34.1 1.0 C19 A:OOK1 2.3 30.5 1.0 C8 A:OOK1 2.4 33.5 1.0 N7 A:OOK1 2.8 32.2 1.0 C10 A:OOK1 3.2 33.0 1.0 C6 A:OOK1 3.5 29.6 1.0 C16 A:OOK1 3.5 34.0 1.0 CD1 A:ILE339 3.6 39.0 1.0 C13 A:OOK1 3.6 33.4 1.0 C4 A:OOK1 3.7 29.0 1.0 C11 A:OOK1 3.7 34.1 1.0 OG A:SER336 3.7 22.8 1.0 CA A:SER336 3.8 23.9 1.0 O21 A:OOK1 3.8 29.9 1.0 CG2 A:ILE273 3.8 50.9 1.0 F28 A:OOK1 3.8 37.3 1.0 C20 A:OOK1 4.1 33.3 1.0 CB A:SER336 4.2 22.5 1.0 CB A:ILE339 4.2 34.4 1.0 N1 A:OOK1 4.2 29.3 1.0 C18 A:OOK1 4.2 31.6 1.0 CG2 A:ILE339 4.4 34.8 1.0 N A:SER336 4.4 23.9 1.0 C5 A:OOK1 4.4 24.1 1.0 CG1 A:ILE339 4.5 33.4 1.0 C9 A:OOK1 4.5 29.3 1.0 CE A:MET294 4.6 32.8 1.0 O A:ARG335 4.6 26.6 1.0 C14 A:OOK1 4.7 26.6 1.0 CD1 A:ILE273 4.7 56.6 1.0 C A:ARG335 4.8 26.3 1.0 O A:SER336 4.8 28.5 1.0 F27 A:OOK1 4.8 35.9 1.0 C A:SER336 4.8 29.9 1.0 C15 A:OOK1 4.8 34.8 1.0 CB A:ILE273 4.9 52.9 1.0

Fluorine binding site 2 out of 8 in the Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid


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 Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid within 5.0Å range: probe atom residue distance (Å) B Occ A:F1 b:35.9 occ:1.00 F27 A:OOK1 0.0 35.9 1.0 C11 A:OOK1 1.4 34.1 1.0 C20 A:OOK1 2.4 33.3 1.0 C8 A:OOK1 2.4 33.5 1.0 N7 A:OOK1 2.8 32.2 1.0 C6 A:OOK1 3.4 29.6 1.0 SD A:MET332 3.5 41.7 1.0 O21 A:OOK1 3.5 29.9 1.0 CG A:MET332 3.6 35.7 1.0 CB A:MET294 3.6 28.1 1.0 C13 A:OOK1 3.7 33.4 1.0 N A:ALA295 3.7 25.9 1.0 C12 A:OOK1 3.7 34.1 1.0 C A:MET294 3.7 28.9 1.0 CA A:ALA295 3.9 25.7 1.0 O A:MET294 3.9 29.9 1.0 C19 A:OOK1 4.2 30.5 1.0 CB A:ALA295 4.3 26.0 1.0 CA A:MET294 4.3 25.6 1.0 C9 A:OOK1 4.5 29.3 1.0 CB A:HIS298 4.6 24.5 1.0 CE A:MET294 4.7 32.8 1.0 OG A:SER336 4.7 22.8 1.0 O A:LEU291 4.7 26.5 1.0 CD1 A:LEU291 4.7 26.6 1.0 F26 A:OOK1 4.8 36.2 1.0 CG A:MET294 4.9 31.9 1.0 C24 A:OOK1 4.9 31.5 1.0 C15 A:OOK1 4.9 34.8 1.0 CE A:MET332 4.9 39.4 1.0

Fluorine binding site 3 out of 8 in the Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid


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 Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid within 5.0Å range: probe atom residue distance (Å) B Occ A:F1 b:37.3 occ:1.00 F28 A:OOK1 0.0 37.3 1.0 C16 A:OOK1 1.3 34.0 1.0 C10 A:OOK1 2.3 33.0 1.0 C18 A:OOK1 2.4 31.6 1.0 F29 A:OOK1 2.7 33.8 1.0 CG2 A:ILE339 3.4 34.8 1.0 CG2 A:ILE273 3.4 50.9 1.0 C4 A:OOK1 3.6 29.0 1.0 C14 A:OOK1 3.6 26.6 1.0 CD1 A:ILE277 3.7 44.2 1.0 CG2 A:THR274 3.8 43.0 1.0 F26 A:OOK1 3.8 36.2 1.0 CD1 A:LEU352 4.0 51.6 1.0 C5 A:OOK1 4.1 24.1 1.0 CB A:ILE339 4.3 34.4 1.0 CD1 A:ILE356 4.5 23.1 1.0 CB A:ILE273 4.6 52.9 1.0 CD2 A:LEU352 4.6 52.5 1.0 CG A:LEU352 4.8 51.1 1.0 N A:THR274 4.8 44.9 1.0 N1 A:OOK1 4.9 29.3 1.0 C A:ILE339 4.9 38.7 1.0 CA A:THR274 4.9 44.9 1.0 C A:ILE273 4.9 49.9 1.0 CB A:THR274 5.0 48.9 1.0

Fluorine binding site 4 out of 8 in the Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid within 5.0Å range: probe atom residue distance (Å) B Occ A:F1 b:33.8 occ:1.00 F29 A:OOK1 0.0 33.8 1.0 C18 A:OOK1 1.3 31.6 1.0 C14 A:OOK1 2.3 26.6 1.0 C16 A:OOK1 2.4 34.0 1.0 F28 A:OOK1 2.7 37.3 1.0 CA A:PHE340 3.1 36.4 1.0 N A:PHE340 3.2 35.5 1.0 CB A:PHE340 3.3 38.1 1.0 CD1 A:PHE340 3.6 45.0 1.0 O A:SER336 3.6 28.5 1.0 C5 A:OOK1 3.6 24.1 1.0 C10 A:OOK1 3.6 33.0 1.0 C A:ILE339 3.8 38.7 1.0 CD1 A:ILE356 3.8 23.1 1.0 CD2 A:LEU352 3.8 52.5 1.0 CG A:PHE340 3.9 40.6 1.0 C4 A:OOK1 4.1 29.0 1.0 O A:ILE339 4.1 40.4 1.0 CG2 A:ILE339 4.1 34.8 1.0 CG A:LEU352 4.3 51.1 1.0 CD1 A:LEU352 4.4 51.6 1.0 CB A:ILE339 4.5 34.4 1.0 C A:PHE340 4.5 43.6 1.0 C A:SER336 4.6 29.9 1.0 CA A:ILE339 4.7 32.2 1.0 CE1 A:PHE340 4.8 46.4 1.0 N3 A:OOK1 4.8 25.0 1.0 CG2 A:THR274 5.0 43.0 1.0 O A:PHE340 5.0 41.4 1.0

Fluorine binding site 5 out of 8 in the Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 5 of Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid within 5.0Å range: probe atom residue distance (Å) B Occ C:F2 b:40.0 occ:1.00 F26 C:OOK2 0.0 40.0 1.0 C12 C:OOK2 1.3 39.6 1.0 C19 C:OOK2 2.3 40.5 1.0 C8 C:OOK2 2.4 40.2 1.0 N7 C:OOK2 2.8 42.0 1.0 C10 C:OOK2 3.3 27.5 1.0 OG C:SER336 3.4 25.1 1.0 C6 C:OOK2 3.4 39.9 1.0 CD1 C:ILE339 3.4 47.0 1.0 CA C:SER336 3.5 26.0 1.0 C13 C:OOK2 3.6 39.0 1.0 C16 C:OOK2 3.6 29.4 1.0 C11 C:OOK2 3.7 37.5 1.0 O21 C:OOK2 3.7 38.1 1.0 C4 C:OOK2 3.7 26.6 1.0 CB C:SER336 3.8 24.4 1.0 CG2 C:ILE273 3.8 59.2 1.0 F28 C:OOK2 4.0 34.4 1.0 C20 C:OOK2 4.1 37.0 1.0 N C:SER336 4.1 27.3 1.0 CB C:ILE339 4.2 41.6 1.0 N1 C:OOK2 4.2 32.1 1.0 C18 C:OOK2 4.3 29.9 1.0 CG1 C:ILE339 4.4 42.3 1.0 C5 C:OOK2 4.4 26.5 1.0 CG2 C:ILE339 4.5 42.7 1.0 C9 C:OOK2 4.5 38.2 1.0 O C:ARG335 4.6 29.0 1.0 C C:SER336 4.6 30.3 1.0 O C:SER336 4.6 31.1 1.0 C C:ARG335 4.6 30.2 1.0 C14 C:OOK2 4.6 27.2 1.0 CE C:MET294 4.8 44.8 1.0 F27 C:OOK2 4.8 36.2 1.0 C15 C:OOK2 4.8 39.7 1.0 CD1 C:ILE273 4.8 66.5 1.0 CB C:ILE273 4.9 58.7 1.0

Fluorine binding site 6 out of 8 in the Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 6 of Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid within 5.0Å range: probe atom residue distance (Å) B Occ C:F2 b:36.2 occ:1.00 F27 C:OOK2 0.0 36.2 1.0 C11 C:OOK2 1.3 37.5 1.0 C20 C:OOK2 2.4 37.0 1.0 C8 C:OOK2 2.4 40.2 1.0 N7 C:OOK2 2.8 42.0 1.0 C6 C:OOK2 3.4 39.9 1.0 CB C:MET294 3.5 38.5 1.0 O21 C:OOK2 3.6 38.1 1.0 C13 C:OOK2 3.6 39.0 1.0 C12 C:OOK2 3.6 39.6 1.0 N C:ALA295 3.7 32.2 1.0 CG C:MET332 3.7 42.9 1.0 C C:MET294 3.8 36.9 1.0 SD C:MET332 3.9 48.9 1.0 CA C:ALA295 3.9 30.9 1.0 O C:MET294 4.1 35.2 1.0 C19 C:OOK2 4.1 40.5 1.0 CB C:ALA295 4.2 31.0 1.0 CA C:MET294 4.3 35.8 1.0 CD1 C:LEU291 4.3 33.5 1.0 O C:LEU291 4.5 36.4 1.0 C9 C:OOK2 4.5 38.2 1.0 CE C:MET294 4.6 44.8 1.0 OG C:SER336 4.7 25.1 1.0 CG C:MET294 4.7 42.7 1.0 F26 C:OOK2 4.8 40.0 1.0 C15 C:OOK2 4.9 39.7 1.0 CB C:HIS298 4.9 27.1 1.0 C24 C:OOK2 5.0 37.4 1.0 O C:HOH30 5.0 34.9 1.0

Fluorine binding site 7 out of 8 in the Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 7 of Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid within 5.0Å range: probe atom residue distance (Å) B Occ C:F2 b:34.4 occ:1.00 F28 C:OOK2 0.0 34.4 1.0 C16 C:OOK2 1.3 29.4 1.0 C10 C:OOK2 2.4 27.5 1.0 C18 C:OOK2 2.4 29.9 1.0 F29 C:OOK2 2.7 37.5 1.0 CG2 C:ILE339 3.4 42.7 1.0 CG2 C:ILE273 3.4 59.2 1.0 CD1 C:ILE277 3.5 57.0 1.0 C4 C:OOK2 3.6 26.6 1.0 C14 C:OOK2 3.6 27.2 1.0 CG2 C:THR274 3.9 47.0 1.0 F26 C:OOK2 4.0 40.0 1.0 CD1 C:LEU352 4.0 38.8 1.0 C5 C:OOK2 4.1 26.5 1.0 CD1 C:ILE356 4.3 47.2 1.0 CB C:ILE339 4.3 41.6 1.0 CB C:ILE273 4.6 58.7 1.0 CD2 C:LEU352 4.7 42.8 1.0 N C:THR274 4.7 48.6 1.0 C C:ILE273 4.8 54.7 1.0 CG C:LEU352 4.8 40.6 1.0 CA C:THR274 4.8 48.0 1.0 N1 C:OOK2 4.9 32.1 1.0 CG1 C:ILE277 5.0 55.5 1.0

Fluorine binding site 8 out of 8 in the Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 8 of Crystal Structure of Human Fxr in Complex with 4-({(2S)-2-[2-(4- Chlorophenyl)-5,6-Difluoro-1H-Benzimidazol-1-Yl]-2- Cyclohexylacetyl}Amino)-3,5-Difluorobenzoic Acid within 5.0Å range: probe atom residue distance (Å) B Occ C:F2 b:37.5 occ:1.00 F29 C:OOK2 0.0 37.5 1.0 C18 C:OOK2 1.3 29.9 1.0 C16 C:OOK2 2.3 29.4 1.0 C14 C:OOK2 2.3 27.2 1.0 F28 C:OOK2 2.7 34.4 1.0 CA C:PHE340 3.1 40.8 1.0 N C:PHE340 3.1 39.8 1.0 CB C:PHE340 3.3 43.0 1.0 O C:SER336 3.5 31.1 1.0 C10 C:OOK2 3.6 27.5 1.0 C5 C:OOK2 3.6 26.5 1.0 CD1 C:PHE340 3.8 49.5 1.0 CD2 C:LEU352 3.8 42.8 1.0 C C:ILE339 3.8 42.6 1.0 CD1 C:ILE356 3.8 47.2 1.0 CG2 C:ILE339 4.0 42.7 1.0 CG C:PHE340 4.0 45.6 1.0 C4 C:OOK2 4.1 26.6 1.0 CG C:LEU352 4.3 40.6 1.0 CB C:ILE339 4.3 41.6 1.0 O C:ILE339 4.4 42.8 1.0 CD1 C:LEU352 4.4 38.8 1.0 C C:PHE340 4.6 46.1 1.0 CA C:ILE339 4.6 37.5 1.0 C C:SER336 4.6 30.3 1.0 N3 C:OOK2 4.9 30.8 1.0 CG2 C:THR274 5.0 47.0 1.0

H.G.F.Richter, G.M.Benson, K.H.Bleicher, D.Blum, E.Chaput, N.Clemann, S.Feng, C.Gardes, U.Grether, P.Hartman, B.Kuhn, R.E.Martin, J.M.Plancher, M.G.Rudolph, F.Schuler, S.Taylor. Optimization of A Novel Class of Benzimidazole-Based Farnesoid X Receptor (Fxr) Agonists to Improve Physicochemical and Adme Properties Bioorg.Med.Chem.Lett. V. 21 1134 2011.
ISSN: ISSN 0960-894X
PubMed: 21269824
DOI: 10.1016/J.BMCL.2010.12.123