Arsenic 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:

Fluorine

(F)

8 atoms

Pages:

>>> Page 1 <<< Page 2, Binding sites: 11 - 12;

Binding sites:

The binding sites of Arsenic 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 Arsenic atom.
In total 12 binding sites of Arsenic 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 Arsenic binding site number: 1; 2; 3; 4; 5; 6; 7; 8; 9; 10;

Arsenic binding site 1 out of 12 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 Arsenic with other atoms in the As 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 A:As60 b:126.5 occ:1.00 AS A:CAS60 0.0 126.5 1.0 CE2 A:CAS60 2.0 65.2 1.0 CE1 A:CAS60 2.0 74.3 1.0 SG A:CAS60 2.2 75.5 1.0 CB A:CAS60 3.1 47.8 1.0 CA A:CAS60 3.5 55.9 1.0 CD2 A:LEU51 3.8 51.5 1.0 NE2 A:GLN49 4.0 59.8 1.0 N A:CAS60 4.2 56.6 1.0 O A:GLU59 4.7 53.4 1.0 C A:CAS60 4.7 55.3 1.0 CD A:GLN49 4.7 56.0 1.0 C A:GLU59 4.7 52.9 1.0 O A:CAS60 4.8 56.2 1.0 CA A:LEU51 4.8 53.9 1.0 CB A:LEU51 4.9 57.4 1.0 CB A:LYS55 4.9 59.1 1.0 CD A:LYS55 5.0 67.8 1.0 CG A:LEU51 5.0 56.8 1.0

Arsenic binding site 2 out of 12 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 Arsenic with other atoms in the As 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 A:As89 b:133.9 occ:1.00 AS A:CAS89 0.0 133.9 1.0 CE1 A:CAS89 2.0 74.3 1.0 CE2 A:CAS89 2.0 108.4 1.0 SG A:CAS89 2.2 80.9 1.0 CB A:CAS89 3.1 51.4 1.0 ND1 A:HIS10 3.4 59.6 1.0 CE1 A:HIS10 3.7 57.8 1.0 O A:CAS89 4.2 48.9 1.0 C A:CAS89 4.3 57.4 1.0 CA A:CAS89 4.3 53.1 1.0 CG A:HIS10 4.3 56.1 1.0 OE1 A:GLU91 4.7 59.3 1.0 NE2 A:HIS10 4.7 58.2 1.0 CA A:HIS10 4.7 46.7 1.0 N A:ILE90 4.9 53.3 1.0 CB A:HIS10 4.9 45.5 1.0

Arsenic binding site 3 out of 12 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 Arsenic with other atoms in the As 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 C:As77 b:66.4 occ:1.00 AS C:CAS77 0.0 66.4 1.0 CE2 C:CAS77 2.0 58.9 1.0 CE1 C:CAS77 2.0 56.6 1.0 SG C:CAS77 2.2 55.5 1.0 CB C:CAS77 3.1 46.5 1.0 CA C:CAS77 3.6 40.4 1.0 CA C:GLY106 3.7 42.0 1.0 N C:GLY106 4.0 40.9 1.0 O C:THR105 4.2 42.7 1.0 C C:CAS77 4.3 44.1 1.0 C C:THR105 4.3 43.0 1.0 N C:ASN78 4.4 44.9 1.0 CE2 C:PHE148 4.8 51.2 1.0 N C:CAS77 4.8 34.3 1.0 O C:PHE76 4.9 42.4 1.0 CZ C:PHE148 5.0 55.2 1.0

Arsenic binding site 4 out of 12 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 Arsenic with other atoms in the As 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 D:As60 b:135.2 occ:1.00 AS D:CAS60 0.0 135.2 1.0 CE1 D:CAS60 2.0 69.0 1.0 CE2 D:CAS60 2.0 63.0 1.0 SG D:CAS60 2.2 58.3 1.0 CB D:CAS60 3.1 48.2 1.0 CA D:CAS60 3.3 47.3 1.0 CD2 D:LEU51 3.9 50.7 1.0 N D:CAS60 4.0 46.3 1.0 O D:GLU59 4.2 47.4 1.0 CB D:LYS55 4.3 51.4 1.0 C D:GLU59 4.3 47.6 1.0 CG D:LYS55 4.4 51.3 1.0 C D:CAS60 4.6 51.2 1.0 O D:CAS60 4.9 51.8 1.0 CA D:LEU51 5.0 37.0 1.0 CB D:LEU51 5.0 43.0 1.0 OE1 D:GLN49 5.0 63.0 1.0

Arsenic binding site 5 out of 12 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 Arsenic with other atoms in the As 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 D:As89 b:88.7 occ:1.00 AS D:CAS89 0.0 88.7 1.0 CE2 D:CAS89 2.0 60.7 1.0 CE1 D:CAS89 2.0 87.6 1.0 SG D:CAS89 2.2 67.0 1.0 CB D:CAS89 3.1 51.0 1.0 CA D:CAS89 3.6 47.0 1.0 C D:CAS89 4.2 44.7 1.0 N D:ILE90 4.3 46.3 1.0 N D:CAS89 4.9 44.0 1.0 O D:LEU88 4.9 48.4 1.0 O D:ILE90 5.0 42.5 1.0

Arsenic binding site 6 out of 12 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 Arsenic with other atoms in the As 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 F:As77 b:62.5 occ:1.00 AS F:CAS77 0.0 62.5 1.0 CE1 F:CAS77 2.0 48.2 1.0 CE2 F:CAS77 2.0 61.6 1.0 SG F:CAS77 2.2 47.4 1.0 CB F:CAS77 3.1 41.5 1.0 CA F:CAS77 3.5 39.4 1.0 CA F:GLY106 3.8 36.7 1.0 N F:GLY106 4.0 44.3 1.0 O F:THR105 4.1 38.1 1.0 C F:THR105 4.2 41.3 1.0 C F:CAS77 4.2 37.8 1.0 N F:ASN78 4.4 36.5 1.0 N F:CAS77 4.8 37.2 1.0 CZ F:PHE148 5.0 54.8 1.0 O F:PHE76 5.0 34.6 1.0 O F:CAS77 5.0 32.8 1.0

Arsenic binding site 7 out of 12 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 Arsenic with other atoms in the As 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 G:As60 b:115.3 occ:1.00 AS G:CAS60 0.0 115.3 1.0 CE1 G:CAS60 2.0 76.7 1.0 CE2 G:CAS60 2.0 64.6 1.0 SG G:CAS60 2.2 51.4 1.0 CB G:CAS60 3.1 44.1 1.0 CA G:CAS60 3.4 43.8 1.0 CD2 G:LEU51 3.9 52.9 1.0 N G:CAS60 4.1 42.0 1.0 CB G:LYS55 4.3 58.2 1.0 O G:GLU59 4.4 50.3 1.0 C G:GLU59 4.5 40.2 1.0 CG G:LYS55 4.5 61.5 1.0 C G:CAS60 4.7 52.0 1.0 NE2 G:GLN49 4.7 51.9 1.0 CA G:LEU51 4.8 64.2 1.0 CB G:LEU51 4.8 55.9 1.0 CG G:LEU51 5.0 55.3 1.0 O G:CAS60 5.0 50.6 1.0

Arsenic binding site 8 out of 12 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 Arsenic with other atoms in the As 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 G:As89 b:147.6 occ:1.00 AS G:CAS89 0.0 147.6 1.0 CE1 G:CAS89 2.0 99.2 1.0 CE2 G:CAS89 2.0 79.9 1.0 SG G:CAS89 2.2 80.7 1.0 CB G:CAS89 3.2 82.4 1.0 CA G:CAS89 3.8 78.5 1.0 C G:CAS89 4.4 71.5 1.0 N G:ILE90 4.5 69.5 1.0

Arsenic binding site 9 out of 12 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 Arsenic with other atoms in the As binding site number 9 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:As77 b:67.5 occ:1.00 AS I:CAS77 0.0 67.5 1.0 CE1 I:CAS77 2.0 61.5 1.0 CE2 I:CAS77 2.0 61.2 1.0 SG I:CAS77 2.2 57.2 1.0 CB I:CAS77 3.1 41.1 1.0 CA I:CAS77 3.7 39.8 1.0 CA I:GLY106 3.9 42.0 1.0 N I:GLY106 4.2 48.9 1.0 C I:CAS77 4.4 37.6 1.0 CZ I:PHE148 4.5 52.2 1.0 C I:THR105 4.5 46.2 1.0 O I:THR105 4.6 47.5 1.0 N I:ASN78 4.7 37.0 1.0 CE1 I:PHE148 4.8 52.2 1.0 N I:CAS77 4.8 43.0 1.0 NE I:ARG79 4.8 61.5 1.0

Arsenic binding site 10 out of 12 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 Arsenic with other atoms in the As binding site number 10 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 J:As60 b:129.2 occ:1.00 AS J:CAS60 0.0 129.2 1.0 CE2 J:CAS60 2.0 52.0 1.0 CE1 J:CAS60 2.0 58.0 1.0 SG J:CAS60 2.2 56.7 1.0 CB J:CAS60 3.1 35.4 1.0 CA J:CAS60 3.3 33.0 1.0 CD2 J:LEU51 3.7 48.8 1.0 N J:CAS60 4.0 39.0 1.0 CB J:LYS55 4.2 46.6 1.0 O J:GLU59 4.2 33.5 1.0 CG J:LYS55 4.3 44.4 1.0 C J:GLU59 4.4 38.4 1.0 C J:CAS60 4.6 40.2 1.0 OE1 J:GLN49 4.7 52.7 1.0 CB J:LEU51 4.7 45.4 1.0 CG J:LEU51 4.8 47.8 1.0 O J:CAS60 4.8 39.9 1.0 CA J:LEU51 4.8 51.6 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