Fluorine in PDB 8cqe: Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37)

The structure of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37), PDB code: 8cqe was solved by R.Casement, L.Phuong Vu, A.Ciulli, M.Gutschow, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	90.05 / 2.85
Space group	P 41 21 2
Cell size a, b, c (Å), α, β, γ (°)	92.971, 92.971, 362.047, 90, 90, 90
R / Rfree (%)	24.3 / 29.7

The structure of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37) also contains other interesting chemical elements:

Arsenic

(As)

12 atoms

The binding sites of Fluorine atom in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37) (pdb code 8cqe). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 8 binding sites of Fluorine where determined in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37), PDB code: 8cqe:
Jump to Fluorine binding site number: 1; 2; 3; 4; 5; 6; 7; 8;

Fluorine binding site 1 out of 8 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37) within 5.0Å range: probe atom residue distance (Å) B Occ C:F301 b:31.2 occ:1.00 F1 C:VFO301 0.0 31.2 1.0 C1 C:VFO301 1.4 36.3 1.0 C2 C:VFO301 2.4 38.9 1.0 C29 C:VFO301 2.4 38.9 1.0 C28 C:VFO301 2.4 37.0 1.0 N1 C:VFO301 2.7 35.6 1.0 OH C:TYR112 2.9 43.0 1.0 CZ C:TYR112 3.1 32.8 1.0 O4 C:VFO301 3.5 39.6 1.0 CE1 C:TYR112 3.5 35.9 1.0 CE2 C:TYR112 3.7 35.1 1.0 C3 C:VFO301 4.1 40.0 1.0 O3 C:VFO301 4.4 33.7 1.0 CD1 C:TYR112 4.4 31.4 1.0 CD2 C:TYR112 4.6 34.2 1.0 C8 C:VFO301 4.6 38.7 1.0 C6 C:VFO301 4.8 20.6 1.0 CG C:TYR112 4.9 29.4 1.0 C4 C:VFO301 5.0 40.0 1.0

Fluorine binding site 2 out of 8 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37) within 5.0Å range: probe atom residue distance (Å) B Occ C:F301 b:32.7 occ:1.00 F2 C:VFO301 0.0 32.7 1.0 C17 C:VFO301 1.4 32.2 1.0 C16 C:VFO301 2.4 29.8 1.0 C18 C:VFO301 2.4 36.2 1.0 S1 C:VFO301 2.6 34.8 1.0 C19 C:VFO301 2.8 35.6 1.0 CD2 C:TYR98 3.5 29.9 1.0 CG2 C:ILE109 3.6 22.5 1.0 CH2 C:TRP117 3.6 27.0 1.0 C23 C:VFO301 3.6 40.4 1.0 C15 C:VFO301 3.6 30.9 1.0 CE2 C:PHE76 3.9 22.3 1.0 CG C:TYR98 4.0 34.8 1.0 CB C:ILE109 4.1 32.8 1.0 C24 C:VFO301 4.1 29.5 1.0 CE2 C:TYR98 4.1 34.4 1.0 C20 C:VFO301 4.2 36.5 1.0 CD1 C:ILE109 4.2 41.7 1.0 CZ3 C:TRP117 4.2 24.1 1.0 CB C:TYR98 4.2 33.2 1.0 C22 C:VFO301 4.3 30.6 1.0 CZ2 C:TRP117 4.4 25.1 1.0 CD2 C:PHE76 4.4 19.5 1.0 CG1 C:ILE109 4.8 32.4 1.0 CZ C:PHE76 4.8 22.6 1.0 N4 C:VFO301 4.8 40.4 1.0 C14 C:VFO301 4.9 35.2 1.0 CD C:PRO99 4.9 30.3 1.0

Fluorine binding site 3 out of 8 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37) within 5.0Å range: probe atom residue distance (Å) B Occ F:F301 b:36.5 occ:1.00 F1 F:VFO301 0.0 36.5 1.0 C1 F:VFO301 1.4 40.8 1.0 C2 F:VFO301 2.4 41.2 1.0 C28 F:VFO301 2.4 45.1 1.0 C29 F:VFO301 2.4 39.5 1.0 N1 F:VFO301 2.7 33.6 1.0 OH F:TYR112 3.0 34.0 1.0 CZ F:TYR112 3.4 31.4 1.0 O4 F:VFO301 3.5 41.7 1.0 CE1 F:TYR112 3.9 34.1 1.0 CE2 F:TYR112 4.1 35.0 1.0 C3 F:VFO301 4.1 35.4 1.0 O3 F:VFO301 4.4 32.3 1.0 C8 F:VFO301 4.6 36.1 1.0 C6 F:VFO301 4.8 24.8 1.0 CD1 F:TYR112 4.9 35.2 1.0 C4 F:VFO301 5.0 33.1 1.0

Fluorine binding site 4 out of 8 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37) within 5.0Å range: probe atom residue distance (Å) B Occ F:F301 b:32.7 occ:1.00 F2 F:VFO301 0.0 32.7 1.0 C17 F:VFO301 1.4 32.8 1.0 C16 F:VFO301 2.4 27.7 1.0 C18 F:VFO301 2.4 36.8 1.0 S1 F:VFO301 2.7 32.3 1.0 C19 F:VFO301 2.8 34.2 1.0 CH2 F:TRP117 3.4 21.9 1.0 CD2 F:TYR98 3.5 28.3 1.0 C15 F:VFO301 3.6 34.7 1.0 C23 F:VFO301 3.6 39.5 1.0 CG F:TYR98 3.8 31.3 1.0 CB F:TYR98 3.9 28.2 1.0 CZ3 F:TRP117 4.1 26.3 1.0 CE2 F:PHE76 4.1 24.6 1.0 CG2 F:ILE109 4.1 32.7 1.0 CE2 F:TYR98 4.1 32.4 1.0 C24 F:VFO301 4.1 32.3 1.0 C20 F:VFO301 4.2 32.8 1.0 CZ2 F:TRP117 4.2 21.1 1.0 C22 F:VFO301 4.3 31.6 1.0 CB F:ILE109 4.4 39.0 1.0 CD1 F:ILE109 4.5 48.2 1.0 CD1 F:TYR98 4.7 33.1 1.0 CD2 F:PHE76 4.8 28.8 1.0 N4 F:VFO301 4.8 40.6 1.0 CZ F:PHE76 4.8 28.1 1.0 C14 F:VFO301 4.9 32.1 1.0 CZ F:TYR98 4.9 33.8 1.0 N3 F:VFO301 5.0 33.6 1.0 CG1 F:ILE109 5.0 34.7 1.0

Fluorine binding site 5 out of 8 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 5 of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37) within 5.0Å range: probe atom residue distance (Å) B Occ I:F301 b:47.1 occ:1.00 F1 I:VFO301 0.0 47.1 1.0 C1 I:VFO301 1.4 39.9 1.0 C2 I:VFO301 2.4 37.3 1.0 C29 I:VFO301 2.4 32.4 1.0 C28 I:VFO301 2.4 34.0 1.0 N1 I:VFO301 2.7 32.4 1.0 O4 I:VFO301 3.5 34.4 1.0 C3 I:VFO301 4.0 30.1 1.0 C6 I:VFO301 4.2 23.0 1.0 C7 I:VFO301 4.2 20.9 1.0 OH I:TYR112 4.3 27.0 1.0 C4 I:VFO301 4.4 33.5 1.0 CZ I:TYR112 4.6 34.6 1.0 CE1 I:TYR112 4.8 36.6 1.0

Fluorine binding site 6 out of 8 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 6 of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37) within 5.0Å range: probe atom residue distance (Å) B Occ I:F301 b:55.1 occ:1.00 F2 I:VFO301 0.0 55.1 1.0 C17 I:VFO301 1.4 41.9 1.0 C16 I:VFO301 2.4 33.2 1.0 C18 I:VFO301 2.4 37.2 1.0 S1 I:VFO301 2.6 66.5 1.0 C19 I:VFO301 2.8 34.6 1.0 CD2 I:TYR98 3.3 33.0 1.0 CH2 I:TRP117 3.5 21.9 1.0 C15 I:VFO301 3.6 33.4 1.0 C23 I:VFO301 3.6 27.4 1.0 CG2 I:ILE109 3.8 35.1 1.0 CG I:TYR98 3.8 28.7 1.0 CE2 I:TYR98 3.9 38.2 1.0 CB I:TYR98 4.0 29.6 1.0 CZ3 I:TRP117 4.1 24.7 1.0 CD1 I:ILE109 4.1 44.8 1.0 C24 I:VFO301 4.1 29.4 1.0 CB I:ILE109 4.1 46.6 1.0 CE2 I:PHE76 4.1 24.3 1.0 C20 I:VFO301 4.2 28.6 1.0 C22 I:VFO301 4.3 44.0 1.0 CZ2 I:TRP117 4.3 25.6 1.0 CD1 I:TYR98 4.7 32.6 1.0 CD2 I:PHE76 4.7 29.1 1.0 CG1 I:ILE109 4.8 43.1 1.0 CZ I:TYR98 4.8 32.5 1.0 N4 I:VFO301 4.8 38.1 1.0 C14 I:VFO301 4.9 26.6 1.0 N3 I:VFO301 5.0 26.5 1.0

Fluorine binding site 7 out of 8 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 7 of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37) within 5.0Å range: probe atom residue distance (Å) B Occ L:F301 b:46.0 occ:1.00 F1 L:VFO301 0.0 46.0 1.0 C1 L:VFO301 1.4 44.7 1.0 C2 L:VFO301 2.4 37.4 1.0 C29 L:VFO301 2.4 55.2 1.0 C28 L:VFO301 2.4 59.7 1.0 N1 L:VFO301 2.7 37.0 1.0 OH L:TYR112 2.9 37.4 1.0 CZ L:TYR112 3.2 37.5 1.0 O4 L:VFO301 3.5 41.1 1.0 CE1 L:TYR112 3.6 41.1 1.0 CE2 L:TYR112 3.8 35.1 1.0 C3 L:VFO301 4.1 41.4 1.0 CD1 L:TYR112 4.5 31.8 1.0 O3 L:VFO301 4.5 38.9 1.0 CD2 L:TYR112 4.7 35.2 1.0 C6 L:VFO301 4.7 26.2 1.0 C8 L:VFO301 4.7 41.1 1.0 C4 L:VFO301 4.9 39.2 1.0

Fluorine binding site 8 out of 8 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 8 of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane- 1-Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-((S)-1-(2-Methyl-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)Pyrrolidine-2-Carboxamide (Compound 37) within 5.0Å range: probe atom residue distance (Å) B Occ L:F301 b:36.0 occ:1.00 F2 L:VFO301 0.0 36.0 1.0 C17 L:VFO301 1.4 38.8 1.0 C16 L:VFO301 2.4 35.8 1.0 C18 L:VFO301 2.4 37.8 1.0 S1 L:VFO301 2.7 42.3 1.0 C19 L:VFO301 2.8 31.0 1.0 CD2 L:TYR98 3.6 24.8 1.0 CH2 L:TRP117 3.6 21.8 1.0 C15 L:VFO301 3.6 33.1 1.0 C23 L:VFO301 3.6 32.0 1.0 CD1 L:ILE109 3.7 42.2 1.0 CG2 L:ILE109 3.9 33.6 1.0 CG L:TYR98 4.0 31.7 1.0 CB L:ILE109 4.1 37.9 1.0 C24 L:VFO301 4.1 31.7 1.0 CE2 L:TYR98 4.1 28.1 1.0 C20 L:VFO301 4.2 38.5 1.0 CZ3 L:TRP117 4.2 29.2 1.0 CB L:TYR98 4.2 25.9 1.0 C22 L:VFO301 4.3 39.8 1.0 CE2 L:PHE76 4.3 29.4 1.0 CZ2 L:TRP117 4.4 22.8 1.0 CG1 L:ILE109 4.5 33.6 1.0 N4 L:VFO301 4.8 39.1 1.0 C14 L:VFO301 4.9 36.1 1.0 CD1 L:TYR98 4.9 40.9 1.0 CD2 L:PHE76 5.0 31.0 1.0 N3 L:VFO301 5.0 34.7 1.0

L.P.Vu, C.J.Diehl, R.Casement, A.G.Bond, C.Steinebach, N.Strasek, A.Bricelj, A.Perdih, G.Schnakenburg, I.Sosic, A.Ciulli, M.Gutschow. Expanding the Structural Diversity at the Phenylene Core of Ligands For the Von Hippel-Lindau E3 Ubiquitin Ligase: Development of Highly Potent Hypoxia-Inducible Factor-1 Alpha Stabilizers. J.Med.Chem. 2023.
ISSN: ISSN 0022-2623
PubMed: 37708384
DOI: 10.1021/ACS.JMEDCHEM.3C00434