Fluorine in PDB 5nvx: Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Fluorocyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 10)

The structure of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Fluorocyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 10), PDB code: 5nvx was solved by M.S.Gadd, P.Soares, C.Galdeano, A.Ciulli, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	49.00 / 2.20
Space group	P 41 2 2
Cell size a, b, c (Å), α, β, γ (°)	93.445, 93.445, 365.195, 90.00, 90.00, 90.00
R / Rfree (%)	19.7 / 24.5

The structure of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Fluorocyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 10) 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- Fluorocyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 10) (pdb code 5nvx). 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- Fluorocyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 10), PDB code: 5nvx:
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- Fluorocyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 10)


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- Fluorocyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 10) within 5.0Å range: probe atom residue distance (Å) B Occ C:F301 b:26.3 occ:1.00 FAI C:4YY301 0.0 26.3 1.0 CBJ C:4YY301 1.3 26.0 1.0 CAP C:4YY301 2.4 24.6 1.0 CAY C:4YY301 2.4 26.0 1.0 CAO C:4YY301 2.4 25.0 1.0 NAV C:4YY301 2.6 24.7 1.0 OAF C:4YY301 3.5 28.8 1.0 OH C:TYR112 3.6 31.2 1.0 CZ C:TYR112 4.0 28.3 1.0 CBG C:4YY301 4.1 26.2 1.0 CE1 C:TYR112 4.3 27.5 1.0 O C:HOH418 4.4 50.3 1.0 OAG C:4YY301 4.5 26.2 1.0 CAC C:4YY301 4.6 24.6 1.0 CE2 C:TYR112 4.6 27.8 1.0 CAZ C:4YY301 4.7 27.5 1.0 CBI C:4YY301 4.8 26.4 1.0 CAD C:4YY301 4.9 26.9 1.0

Fluorine binding site 2 out of 4 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Fluorocyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 10)


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- Fluorocyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 10) within 5.0Å range: probe atom residue distance (Å) B Occ F:F301 b:31.3 occ:1.00 FAI F:4YY301 0.0 31.3 1.0 CBJ F:4YY301 1.3 32.3 1.0 CAY F:4YY301 2.4 29.1 1.0 CAO F:4YY301 2.4 33.2 1.0 CAP F:4YY301 2.5 31.8 1.0 NAV F:4YY301 2.6 28.3 1.0 OAF F:4YY301 3.5 31.7 1.0 OH F:TYR112 3.6 38.7 1.0 CBG F:4YY301 4.1 29.2 1.0 CZ F:TYR112 4.1 36.9 1.0 CAC F:4YY301 4.4 28.9 1.0 CE1 F:TYR112 4.4 33.5 1.0 OAG F:4YY301 4.5 27.5 1.0 CBI F:4YY301 4.7 30.3 1.0 CAZ F:4YY301 4.7 29.1 1.0 CE2 F:TYR112 4.8 38.1 1.0 CAD F:4YY301 4.8 35.2 1.0

Fluorine binding site 3 out of 4 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Fluorocyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 10)


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- Fluorocyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 10) within 5.0Å range: probe atom residue distance (Å) B Occ I:F301 b:33.4 occ:1.00 FAI I:4YY301 0.0 33.4 1.0 CBJ I:4YY301 1.3 35.4 1.0 CAY I:4YY301 2.4 31.9 1.0 CAO I:4YY301 2.5 33.6 1.0 CAP I:4YY301 2.5 34.3 1.0 NAV I:4YY301 2.7 31.5 1.0 O I:HOH410 3.4 45.1 1.0 OH I:TYR112 3.4 32.3 1.0 OAF I:4YY301 3.6 32.3 1.0 CZ I:TYR112 3.9 31.6 1.0 CBG I:4YY301 4.1 30.7 1.0 CE1 I:TYR112 4.4 30.2 1.0 OAG I:4YY301 4.5 26.2 1.0 CE2 I:TYR112 4.6 32.6 1.0 CAC I:4YY301 4.6 28.7 1.0 CAZ I:4YY301 4.8 29.2 1.0 CBI I:4YY301 4.8 30.8 1.0 CAD I:4YY301 4.9 30.7 1.0

Fluorine binding site 4 out of 4 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Fluorocyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 10)


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- Fluorocyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 10) within 5.0Å range: probe atom residue distance (Å) B Occ L:F301 b:32.4 occ:1.00 FAI L:4YY301 0.0 32.4 1.0 CBJ L:4YY301 1.2 31.4 1.0 CAO L:4YY301 2.3 30.6 1.0 CAY L:4YY301 2.4 28.9 1.0 CAP L:4YY301 2.4 31.3 1.0 NAV L:4YY301 2.6 29.4 1.0 O L:HOH410 3.1 38.1 1.0 OAF L:4YY301 3.5 29.0 1.0 OH L:TYR112 3.5 35.2 1.0 CZ L:TYR112 3.9 33.9 1.0 CBG L:4YY301 4.1 28.6 1.0 CE1 L:TYR112 4.3 31.7 1.0 OAG L:4YY301 4.4 27.5 1.0 CE2 L:TYR112 4.5 35.1 1.0 CAC L:4YY301 4.6 31.4 1.0 CAZ L:4YY301 4.7 28.7 1.0 CBI L:4YY301 4.8 31.6 1.0 CAD L:4YY301 4.9 30.2 1.0

P.Soares, M.S.Gadd, J.Frost, C.Galdeano, L.Ellis, O.Epemolu, S.Rocha, K.D.Read, A.Ciulli. Group-Based Optimization of Potent and Cell-Active Inhibitors of the Von Hippel-Lindau (Vhl) E3 Ubiquitin Ligase: Structure-Activity Relationships Leading to the Chemical Probe (2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3, 3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl) Benzyl)Pyrrolidine-2-Carboxamide (VH298). J. Med. Chem. V. 61 599 2018.
ISSN: ISSN 1520-4804
PubMed: 28853884
DOI: 10.1021/ACS.JMEDCHEM.7B00675