Fluorine in PDB 8cql: Pvhl:Elob:Eloc in Complex with (2S,4R)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33)

The structure of Pvhl:Elob:Eloc in Complex with (2S,4R)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33), PDB code: 8cql 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)	64.53 / 2.38
Space group	P 41 21 2
Cell size a, b, c (Å), α, β, γ (°)	92.688, 92.688, 359.622, 90, 90, 90
R / Rfree (%)	22.6 / 27.5

The structure of Pvhl:Elob:Eloc in Complex with (2S,4R)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33) 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)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33) (pdb code 8cql). 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)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33), PDB code: 8cql:
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)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33)


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)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33) within 5.0Å range: probe atom residue distance (Å) B Occ C:F301 b:41.9 occ:1.00 F21 C:VH3301 0.0 41.9 1.0 C20 C:VH3301 1.4 40.4 1.0 C22 C:VH3301 2.4 36.0 1.0 C13 C:VH3301 2.4 37.2 1.0 C14 C:VH3301 2.8 38.2 1.0 S19 C:VH3301 2.9 42.7 1.0 CB C:ILE109 3.2 41.5 1.0 CG2 C:ILE109 3.3 34.0 1.0 CG1 C:ILE109 3.6 42.0 1.0 C08 C:VH3301 3.7 40.2 1.0 C12 C:VH3301 3.7 41.3 1.0 CD1 C:ILE109 3.7 39.9 1.0 CE2 C:PHE76 3.7 38.2 1.0 CH2 C:TRP117 3.8 32.6 1.0 C15 C:VH3301 4.1 40.3 1.0 CD2 C:TYR98 4.1 36.6 1.0 C09 C:VH3301 4.2 39.7 1.0 C18 C:VH3301 4.3 37.6 1.0 CD2 C:PHE76 4.3 33.2 1.0 CZ2 C:TRP117 4.4 24.8 1.0 CZ C:PHE76 4.4 31.5 1.0 CE2 C:TYR98 4.5 29.3 1.0 CA C:ILE109 4.6 43.4 1.0 CZ3 C:TRP117 4.6 31.1 1.0 N06 C:VH3301 4.7 34.1 1.0 N17 C:VH3301 4.8 35.1 1.0 CG C:TYR98 4.9 39.7 1.0 O C:HIS110 4.9 33.2 1.0 C07 C:VH3301 4.9 44.6 1.0 O C:HOH428 5.0 37.8 1.0 N C:HIS110 5.0 44.9 1.0

Fluorine binding site 2 out of 8 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33)


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)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33) within 5.0Å range: probe atom residue distance (Å) B Occ C:F301 b:55.2 occ:1.00 F35 C:VH3301 0.0 55.2 1.0 C34 C:VH3301 1.4 44.2 1.0 C37 C:VH3301 2.5 56.6 1.0 C36 C:VH3301 2.5 45.2 1.0 C33 C:VH3301 2.5 48.1 1.0 N32 C:VH3301 2.9 51.5 1.0 OH C:TYR112 3.5 61.0 1.0 O38 C:VH3301 3.6 48.9 1.0 CZ C:TYR112 3.8 43.0 1.0 CE1 C:TYR112 4.2 44.1 1.0 CE2 C:TYR112 4.3 38.5 1.0 C27 C:VH3301 4.4 43.9 1.0 O39 C:VH3301 4.7 44.7 1.0 C30 C:VH3301 4.9 35.1 1.0 C26 C:VH3301 4.9 41.6 1.0

Fluorine binding site 3 out of 8 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33)


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)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33) within 5.0Å range: probe atom residue distance (Å) B Occ F:F301 b:37.8 occ:1.00 F21 F:VH3301 0.0 37.8 1.0 C20 F:VH3301 1.4 39.7 1.0 C22 F:VH3301 2.4 33.7 1.0 C13 F:VH3301 2.4 37.7 1.0 C14 F:VH3301 2.8 40.0 1.0 S19 F:VH3301 2.9 36.3 1.0 CB F:ILE109 3.1 38.9 1.0 CG2 F:ILE109 3.2 36.8 1.0 CG1 F:ILE109 3.5 38.2 1.0 CD1 F:ILE109 3.6 36.6 1.0 C08 F:VH3301 3.7 35.2 1.0 C12 F:VH3301 3.7 37.7 1.0 CE2 F:PHE76 3.8 33.5 1.0 CH2 F:TRP117 3.9 30.9 1.0 C15 F:VH3301 4.1 40.8 1.0 CD2 F:TYR98 4.1 31.9 1.0 C09 F:VH3301 4.2 41.8 1.0 CZ2 F:TRP117 4.3 23.4 1.0 CD2 F:PHE76 4.3 29.9 1.0 C18 F:VH3301 4.4 35.9 1.0 CZ F:PHE76 4.4 26.2 1.0 CA F:ILE109 4.4 37.6 1.0 CE2 F:TYR98 4.5 33.8 1.0 CZ3 F:TRP117 4.7 27.2 1.0 N06 F:VH3301 4.7 34.8 1.0 N17 F:VH3301 4.8 41.4 1.0 N F:HIS110 4.9 39.6 1.0 C07 F:VH3301 4.9 39.5 1.0 CG F:TYR98 4.9 37.7 1.0 O F:HIS110 4.9 30.0 1.0

Fluorine binding site 4 out of 8 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33)


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)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33) within 5.0Å range: probe atom residue distance (Å) B Occ F:F301 b:49.4 occ:1.00 F35 F:VH3301 0.0 49.4 1.0 C34 F:VH3301 1.4 45.9 1.0 C37 F:VH3301 2.5 46.1 1.0 C36 F:VH3301 2.5 43.7 1.0 C33 F:VH3301 2.5 47.3 1.0 N32 F:VH3301 2.9 39.9 1.0 OH F:TYR112 3.4 51.0 1.0 O38 F:VH3301 3.6 37.2 1.0 CZ F:TYR112 3.9 43.0 1.0 CE1 F:TYR112 4.3 40.0 1.0 C27 F:VH3301 4.3 37.8 1.0 CE2 F:TYR112 4.5 33.0 1.0 O39 F:VH3301 4.7 35.6 1.0 C31 F:VH3301 4.9 26.1 1.0 C26 F:VH3301 4.9 43.5 1.0

Fluorine binding site 5 out of 8 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33)


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)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33) within 5.0Å range: probe atom residue distance (Å) B Occ I:F301 b:38.5 occ:1.00 F21 I:VH3301 0.0 38.5 1.0 C20 I:VH3301 1.4 45.1 1.0 C13 I:VH3301 2.4 45.7 1.0 C22 I:VH3301 2.4 40.4 1.0 C14 I:VH3301 2.8 46.3 1.0 S19 I:VH3301 3.1 47.3 1.0 CB I:ILE109 3.2 42.5 1.0 CG2 I:ILE109 3.3 40.3 1.0 CD1 I:ILE109 3.3 40.0 1.0 CG1 I:ILE109 3.4 43.6 1.0 C12 I:VH3301 3.7 46.9 1.0 C08 I:VH3301 3.7 47.2 1.0 CE2 I:PHE76 3.7 35.9 1.0 C15 I:VH3301 4.0 43.2 1.0 CH2 I:TRP117 4.0 29.9 1.0 C09 I:VH3301 4.2 47.1 1.0 CD2 I:TYR98 4.2 38.5 1.0 CD2 I:PHE76 4.3 35.0 1.0 CZ I:PHE76 4.4 41.7 1.0 C18 I:VH3301 4.4 41.8 1.0 CZ2 I:TRP117 4.4 31.6 1.0 CA I:ILE109 4.6 39.4 1.0 CZ3 I:TRP117 4.7 40.6 1.0 CE2 I:TYR98 4.7 43.6 1.0 N17 I:VH3301 4.8 48.4 1.0 N06 I:VH3301 4.8 43.1 1.0 C16 I:VH3301 4.8 42.2 1.0 C07 I:VH3301 4.9 46.0 1.0 N I:HIS110 5.0 42.8 1.0 CG I:TYR98 5.0 43.1 1.0

Fluorine binding site 6 out of 8 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33)


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)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33) within 5.0Å range: probe atom residue distance (Å) B Occ I:F301 b:64.3 occ:1.00 F35 I:VH3301 0.0 64.3 1.0 C34 I:VH3301 1.4 55.7 1.0 C36 I:VH3301 2.5 51.6 1.0 C37 I:VH3301 2.5 54.6 1.0 C33 I:VH3301 2.5 50.0 1.0 N32 I:VH3301 2.9 51.4 1.0 OH I:TYR112 3.3 47.1 1.0 O I:HOH416 3.4 45.7 1.0 O38 I:VH3301 3.6 51.3 1.0 CZ I:TYR112 3.7 45.3 1.0 CE2 I:TYR112 4.0 50.3 1.0 CE1 I:TYR112 4.4 47.1 1.0 C27 I:VH3301 4.4 44.7 1.0 O39 I:VH3301 4.8 49.1 1.0 C31 I:VH3301 4.9 47.2 1.0 CD2 I:TYR112 5.0 45.5 1.0 C26 I:VH3301 5.0 47.9 1.0

Fluorine binding site 7 out of 8 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33)


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)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33) within 5.0Å range: probe atom residue distance (Å) B Occ L:F301 b:37.0 occ:1.00 F21 L:VH3301 0.0 37.0 1.0 C20 L:VH3301 1.4 40.3 1.0 C13 L:VH3301 2.4 40.3 1.0 C22 L:VH3301 2.4 34.7 1.0 C14 L:VH3301 2.8 41.6 1.0 S19 L:VH3301 3.0 40.7 1.0 CB L:ILE109 3.2 43.7 1.0 CG2 L:ILE109 3.3 36.2 1.0 CG1 L:ILE109 3.5 49.5 1.0 CE2 L:PHE76 3.6 28.3 1.0 CD1 L:ILE109 3.6 44.6 1.0 C12 L:VH3301 3.7 35.3 1.0 C08 L:VH3301 3.7 39.7 1.0 CH2 L:TRP117 3.8 29.1 1.0 CD2 L:TYR98 4.0 39.8 1.0 C15 L:VH3301 4.1 41.5 1.0 C09 L:VH3301 4.1 33.6 1.0 CD2 L:PHE76 4.2 29.3 1.0 CZ2 L:TRP117 4.3 32.8 1.0 C18 L:VH3301 4.4 45.4 1.0 CZ L:PHE76 4.4 30.3 1.0 CE2 L:TYR98 4.5 39.5 1.0 CZ3 L:TRP117 4.5 30.9 1.0 CA L:ILE109 4.6 38.6 1.0 CG L:TYR98 4.7 38.0 1.0 N06 L:VH3301 4.8 34.5 1.0 N17 L:VH3301 4.8 41.6 1.0 C07 L:VH3301 4.9 40.4 1.0 CB L:TYR98 4.9 33.6 1.0 C16 L:VH3301 5.0 37.6 1.0

Fluorine binding site 8 out of 8 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33)


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)-N-((S)-1-(5-Fluoro-2-Methoxy-4- (4-Methylthiazol-5-Yl)Phenyl)Ethyl)-1-((S)-2-(1-Fluorocyclopropane-1- Carboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxypyrrolidine-2-Carboxamide (Compound 33) within 5.0Å range: probe atom residue distance (Å) B Occ L:F301 b:51.6 occ:1.00 F35 L:VH3301 0.0 51.6 1.0 C34 L:VH3301 1.4 46.7 1.0 C37 L:VH3301 2.4 44.2 1.0 C36 L:VH3301 2.5 45.2 1.0 C33 L:VH3301 2.5 43.5 1.0 N32 L:VH3301 2.9 41.3 1.0 OH L:TYR112 3.3 44.9 1.0 O38 L:VH3301 3.6 42.5 1.0 CZ L:TYR112 3.7 41.8 1.0 CE2 L:TYR112 4.1 40.0 1.0 C27 L:VH3301 4.4 37.9 1.0 CE1 L:TYR112 4.4 43.0 1.0 O39 L:VH3301 4.8 42.4 1.0 C26 L:VH3301 5.0 45.6 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