Arsenic 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:

Fluorine

(F)

4 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)-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 Arsenic atom.
In total 12 binding sites of Arsenic 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 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)-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 Arsenic with other atoms in the As 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 A:As60 b:138.1 occ:1.00 AS A:CAS60 0.0 138.1 1.0 CE2 A:CAS60 2.0 58.7 1.0 CE1 A:CAS60 2.0 70.5 1.0 SG A:CAS60 2.2 83.0 1.0 CB A:CAS60 3.1 52.5 1.0 CA A:CAS60 3.3 50.7 1.0 CD2 A:LEU51 3.9 52.7 1.0 N A:CAS60 3.9 50.9 1.0 O A:GLU59 4.3 47.2 1.0 CB A:LYS55 4.3 51.6 1.0 C A:GLU59 4.4 49.5 1.0 C A:CAS60 4.6 48.8 1.0 O A:CAS60 4.9 51.7 1.0 NE2 A:GLN49 4.9 57.4 1.0 CA A:LEU51 5.0 52.0 1.0

Arsenic binding site 2 out of 12 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 Arsenic with other atoms in the As 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 A:As89 b:109.9 occ:1.00 AS A:CAS89 0.0 109.9 1.0 CE2 A:CAS89 2.0 71.1 1.0 CE1 A:CAS89 2.0 85.9 1.0 SG A:CAS89 2.2 71.6 1.0 CB A:CAS89 2.9 62.6 1.0 CA A:CAS89 3.5 56.0 1.0 C A:CAS89 4.1 49.4 1.0 N A:ILE90 4.3 51.0 1.0 O A:ILE90 4.8 50.5 1.0 O A:CAS89 4.8 49.8 1.0 N A:CAS89 4.8 53.2 1.0 C A:ILE90 4.8 55.9 1.0 O A:LEU88 5.0 54.4 1.0

Arsenic binding site 3 out of 12 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 Arsenic with other atoms in the As 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 C:As77 b:99.9 occ:1.00 AS C:CAS77 0.0 99.9 1.0 CE2 C:CAS77 2.0 65.8 1.0 CE1 C:CAS77 2.0 67.4 1.0 SG C:CAS77 2.2 76.6 1.0 CB C:CAS77 3.1 49.9 1.0 CA C:CAS77 3.6 48.6 1.0 O C:THR105 4.2 53.4 1.0 C C:CAS77 4.2 45.8 1.0 N C:ASN78 4.3 43.5 1.0 CA C:GLY106 4.6 53.1 1.0 CZ C:PHE148 4.6 57.6 1.0 C C:THR105 4.7 58.3 1.0 N C:GLY106 4.8 59.7 1.0 N C:CAS77 4.9 50.3 1.0

Arsenic binding site 4 out of 12 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 Arsenic with other atoms in the As 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 D:As60 b:104.5 occ:1.00 AS D:CAS60 0.0 104.5 1.0 CE1 D:CAS60 2.0 70.1 1.0 CE2 D:CAS60 2.0 69.8 1.0 SG D:CAS60 2.2 79.8 1.0 CB D:CAS60 3.2 44.6 1.0 CA D:CAS60 3.5 45.6 1.0 CD2 D:LEU51 4.1 57.4 1.0 N D:CAS60 4.1 44.4 1.0 CB D:LYS55 4.5 64.7 1.0 NE2 D:GLN49 4.5 48.7 1.0 CG D:LYS55 4.6 72.9 1.0 O G:GLN65 4.6 47.2 1.0 CG2 G:THR66 4.6 48.5 1.0 C D:GLU59 4.7 43.5 1.0 C D:CAS60 4.7 44.8 1.0 O D:GLU59 4.7 47.4 1.0 CB G:GLN65 4.8 54.5 1.0 O D:CAS60 4.9 39.6 1.0 CD D:GLN49 5.0 51.2 1.0

Arsenic binding site 5 out of 12 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 Arsenic with other atoms in the As 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 30) within 5.0Å range: probe atom residue distance (Å) B Occ D:As89 b:152.1 occ:1.00 AS D:CAS89 0.0 152.1 1.0 CE1 D:CAS89 2.0 112.1 1.0 CE2 D:CAS89 2.0 91.8 1.0 SG D:CAS89 2.2 100.9 1.0 CB D:CAS89 3.0 81.5 1.0 CA D:CAS89 3.6 75.8 1.0 C D:CAS89 4.2 74.6 1.0 N D:ILE90 4.3 73.5 1.0 O D:LEU88 4.7 74.9 1.0 N D:CAS89 4.8 78.7 1.0 O D:ILE90 4.9 65.3 1.0

Arsenic binding site 6 out of 12 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 Arsenic with other atoms in the As 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 30) within 5.0Å range: probe atom residue distance (Å) B Occ F:As77 b:89.4 occ:1.00 AS F:CAS77 0.0 89.4 1.0 CE2 F:CAS77 2.0 61.4 1.0 CE1 F:CAS77 2.0 64.0 1.0 SG F:CAS77 2.2 70.6 1.0 CB F:CAS77 3.1 52.9 1.0 CA F:CAS77 3.6 47.0 1.0 O F:THR105 3.7 45.3 1.0 C F:CAS77 4.1 46.0 1.0 CA F:GLY106 4.2 44.8 1.0 N F:ASN78 4.2 40.8 1.0 C F:THR105 4.3 47.5 1.0 CE K:MET45 4.4 59.9 1.0 N F:GLY106 4.5 50.6 1.0 CZ F:PHE148 4.7 63.8 1.0 NE F:ARG79 4.8 62.3 1.0 N F:CAS77 4.9 45.1 1.0 CG F:ARG79 4.9 54.6 1.0 O F:CAS77 4.9 41.8 1.0 O F:PHE76 5.0 49.3 1.0

Arsenic binding site 7 out of 12 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 Arsenic with other atoms in the As 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 30) within 5.0Å range: probe atom residue distance (Å) B Occ G:As60 b:107.1 occ:1.00 AS G:CAS60 0.0 107.1 1.0 CE1 G:CAS60 2.0 70.6 1.0 CE2 G:CAS60 2.0 61.6 1.0 SG G:CAS60 2.2 65.2 1.0 CB G:CAS60 3.1 52.7 1.0 CA G:CAS60 3.3 52.3 1.0 N G:CAS60 3.9 54.6 1.0 CD2 G:LEU51 4.0 53.9 1.0 O G:GLU59 4.2 50.7 1.0 C G:GLU59 4.3 55.5 1.0 CB G:LYS55 4.4 54.2 1.0 CG2 D:THR66 4.4 49.8 1.0 CG G:LYS55 4.5 54.4 1.0 C G:CAS60 4.6 54.2 1.0 CB D:GLN65 4.8 57.5 1.0 O D:GLN65 4.8 45.3 1.0 NE2 G:GLN49 4.8 46.4 1.0 O G:CAS60 4.9 54.8 1.0

Arsenic binding site 8 out of 12 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 Arsenic with other atoms in the As 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 30) within 5.0Å range: probe atom residue distance (Å) B Occ G:As89 b:100.5 occ:1.00 AS G:CAS89 0.0 100.5 1.0 CE2 G:CAS89 2.0 67.4 1.0 CE1 G:CAS89 2.0 86.7 1.0 SG G:CAS89 2.2 81.1 1.0 CB G:CAS89 3.1 50.5 1.0 CA G:CAS89 3.7 49.8 1.0 C G:CAS89 4.3 51.0 1.0 N G:ILE90 4.3 45.1 1.0 OE2 G:GLU91 4.9 52.2 1.0 N G:CAS89 5.0 42.5 1.0

Arsenic binding site 9 out of 12 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 Arsenic with other atoms in the As binding site number 9 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:As77 b:82.0 occ:1.00 AS I:CAS77 0.0 82.0 1.0 CE2 I:CAS77 2.0 48.9 1.0 CE1 I:CAS77 2.0 46.5 1.0 SG I:CAS77 2.2 52.5 1.0 CB I:CAS77 3.1 49.7 1.0 CA I:CAS77 3.6 44.2 1.0 O I:HOH401 4.1 42.4 1.0 O I:THR105 4.1 47.8 1.0 C I:CAS77 4.2 44.5 1.0 CA I:GLY106 4.3 39.5 1.0 N I:ASN78 4.4 42.3 1.0 C I:THR105 4.4 44.1 1.0 N I:GLY106 4.5 42.5 1.0 CZ I:PHE148 4.8 52.0 1.0 O I:CAS77 4.9 40.0 1.0 NH1 I:ARG79 4.9 50.8 1.0 N I:CAS77 4.9 46.2 1.0 CE2 I:PHE148 4.9 53.7 1.0

Arsenic binding site 10 out of 12 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 Arsenic with other atoms in the As binding site number 10 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 J:As60 b:110.9 occ:1.00 AS J:CAS60 0.0 110.9 1.0 CE1 J:CAS60 2.0 74.0 1.0 CE2 J:CAS60 2.0 67.3 1.0 SG J:CAS60 2.2 80.0 1.0 CB J:CAS60 3.1 49.5 1.0 CA J:CAS60 3.4 56.2 1.0 N J:CAS60 4.1 59.7 1.0 NE2 J:GLN49 4.1 46.3 1.0 CD2 J:LEU51 4.1 52.2 1.0 C J:GLU59 4.6 57.5 1.0 C J:CAS60 4.6 57.4 1.0 O J:GLU59 4.6 55.8 1.0 CD J:GLN49 4.7 45.8 1.0 CB J:LYS55 4.7 62.3 1.0 CG J:LYS55 4.7 60.1 1.0 O J:CAS60 4.8 53.5 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