Fluorine in PDB 8cqk: 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 30)

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 30), PDB code: 8cqk 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)	65.07 / 2.62
Space group	P 41 21 2
Cell size a, b, c (Å), α, β, γ (°)	93.284, 93.284, 363.262, 90, 90, 90
R / Rfree (%)	24.6 / 29

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 30) 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 30) (pdb code 8cqk). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 4 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 30), PDB code: 8cqk:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 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 30)


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 30) within 5.0Å range: probe atom residue distance (Å) B Occ C:F301 b:53.2 occ:1.00 F33 C:VYQ301 0.0 53.2 1.0 C32 C:VYQ301 1.4 55.9 1.0 C35 C:VYQ301 2.4 53.9 1.0 C34 C:VYQ301 2.5 52.4 1.0 C31 C:VYQ301 2.5 54.6 1.0 N30 C:VYQ301 2.9 50.3 1.0 OH C:TYR112 3.4 65.0 1.0 O36 C:VYQ301 3.6 52.5 1.0 CZ C:TYR112 3.9 54.9 1.0 C25 C:VYQ301 4.4 47.7 1.0 CE1 C:TYR112 4.4 51.6 1.0 CE2 C:TYR112 4.5 53.3 1.0 O37 C:VYQ301 4.7 57.5 1.0 C27 C:VYQ301 4.9 57.1 1.0 C24 C:VYQ301 5.0 56.1 1.0

Fluorine binding site 2 out of 4 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 30)


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 30) within 5.0Å range: probe atom residue distance (Å) B Occ F:F301 b:65.1 occ:1.00 F33 F:VYQ301 0.0 65.1 1.0 C32 F:VYQ301 1.4 61.5 1.0 C35 F:VYQ301 2.5 63.1 1.0 C34 F:VYQ301 2.5 59.0 1.0 C31 F:VYQ301 2.5 56.3 1.0 N30 F:VYQ301 2.9 52.1 1.0 OH F:TYR112 3.2 67.0 1.0 O36 F:VYQ301 3.6 52.5 1.0 CZ F:TYR112 3.7 52.4 1.0 CE2 F:TYR112 4.2 53.7 1.0 O F:HOH403 4.2 48.2 1.0 CE1 F:TYR112 4.3 49.4 1.0 C25 F:VYQ301 4.4 54.6 1.0 O37 F:VYQ301 4.7 54.9 1.0 C27 F:VYQ301 4.8 51.6 1.0 C24 F:VYQ301 5.0 55.1 1.0

Fluorine binding site 3 out of 4 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 30)


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 30) within 5.0Å range: probe atom residue distance (Å) B Occ I:F301 b:57.4 occ:1.00 F33 I:VYQ301 0.0 57.4 1.0 C32 I:VYQ301 1.4 55.5 1.0 C35 I:VYQ301 2.5 54.5 1.0 C34 I:VYQ301 2.5 47.4 1.0 C31 I:VYQ301 2.5 60.7 1.0 N30 I:VYQ301 2.9 54.8 1.0 OH I:TYR112 3.5 58.2 1.0 O36 I:VYQ301 3.6 59.0 1.0 CZ I:TYR112 4.0 56.0 1.0 C25 I:VYQ301 4.4 49.8 1.0 CE1 I:TYR112 4.5 58.0 1.0 C27 I:VYQ301 4.6 51.9 1.0 CE2 I:TYR112 4.6 54.4 1.0 O37 I:VYQ301 4.7 54.8 1.0 C24 I:VYQ301 5.0 52.5 1.0

Fluorine binding site 4 out of 4 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 30)


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 30) within 5.0Å range: probe atom residue distance (Å) B Occ L:F301 b:65.9 occ:1.00 F33 L:VYQ301 0.0 65.9 1.0 C32 L:VYQ301 1.4 55.1 1.0 C34 L:VYQ301 2.4 52.2 1.0 C35 L:VYQ301 2.5 48.0 1.0 C31 L:VYQ301 2.5 54.9 1.0 N30 L:VYQ301 2.9 49.6 1.0 O L:HOH411 3.2 56.4 1.0 O36 L:VYQ301 3.6 49.6 1.0 OH L:TYR112 3.7 61.3 1.0 CZ L:TYR112 4.1 49.8 1.0 C25 L:VYQ301 4.4 54.0 1.0 CE1 L:TYR112 4.5 51.7 1.0 CE2 L:TYR112 4.8 44.5 1.0 C27 L:VYQ301 4.8 57.7 1.0 O37 L:VYQ301 4.8 54.4 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