Arsenic in PDB 5nw2: Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19)

The structure of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19), PDB code: 5nw2 was solved by M.S.Gadd, P.Soares, A.Ciulli, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	49.54 / 2.20
Space group	P 41 2 2
Cell size a, b, c (Å), α, β, γ (°)	94.604, 94.604, 368.640, 90.00, 90.00, 90.00
R / Rfree (%)	19.5 / 24.2

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)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19) (pdb code 5nw2). 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)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19), PDB code: 5nw2:
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)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19)


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)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19) within 5.0Å range: probe atom residue distance (Å) B Occ A:As60 b:58.9 occ:1.00 AS A:CAS60 0.0 58.9 1.0 CE1 A:CAS60 2.0 61.7 1.0 CE2 A:CAS60 2.0 58.3 1.0 SG A:CAS60 2.3 40.3 1.0 CB A:CAS60 3.2 33.6 1.0 CA A:CAS60 3.5 31.7 1.0 CD2 A:LEU51 3.7 34.7 1.0 N A:CAS60 4.2 29.1 1.0 O A:GLU59 4.5 30.6 1.0 CB A:LYS55 4.6 30.3 1.0 CG A:LYS55 4.6 34.5 1.0 C A:GLU59 4.7 31.1 1.0 C A:CAS60 4.7 32.3 1.0 O A:CAS60 4.9 33.7 1.0 CA A:LEU51 4.9 36.3 1.0 NE2 A:GLN49 4.9 48.7 1.0 CG A:LEU51 5.0 34.2 1.0 CB A:LEU51 5.0 34.0 1.0

Arsenic binding site 2 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19)


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)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19) within 5.0Å range: probe atom residue distance (Å) B Occ A:As89 b:61.5 occ:1.00 AS A:CAS89 0.0 61.5 1.0 CE1 A:CAS89 2.0 64.8 1.0 CE2 A:CAS89 2.0 60.3 1.0 SG A:CAS89 2.2 52.4 1.0 CB A:CAS89 2.9 48.3 1.0 CA A:CAS89 3.5 44.4 1.0 O A:HOH211 3.9 42.5 1.0 C A:CAS89 4.1 40.9 1.0 N A:ILE90 4.1 40.5 1.0 O A:HOH274 4.6 46.1 1.0 OE2 A:GLU91 4.6 63.2 1.0 O A:HOH299 4.7 56.9 1.0 N A:CAS89 4.8 44.0 1.0 O A:ILE90 4.8 39.3 1.0 O A:LEU88 4.9 47.1 1.0 C A:ILE90 4.9 38.8 1.0 O A:CAS89 5.0 39.5 1.0

Arsenic binding site 3 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19)


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)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19) within 5.0Å range: probe atom residue distance (Å) B Occ C:As77 b:53.5 occ:1.00 AS C:CAS77 0.0 53.5 1.0 CE2 C:CAS77 2.0 54.3 1.0 CE1 C:CAS77 2.0 52.0 1.0 SG C:CAS77 2.2 38.4 1.0 CB C:CAS77 3.1 32.7 1.0 CA C:CAS77 3.6 28.3 1.0 CA C:GLY106 4.1 33.4 1.0 O C:THR105 4.3 32.5 1.0 C C:CAS77 4.4 27.7 1.0 N C:GLY106 4.4 32.4 1.0 C C:THR105 4.5 33.3 1.0 CE2 C:PHE148 4.6 45.7 1.0 N C:ASN78 4.6 26.7 1.0 CZ K:PHE109 4.6 33.9 1.0 N C:CAS77 4.8 26.7 1.0 CE K:MET45 4.8 77.0 1.0 O C:PHE76 4.9 27.0 1.0 NH2 C:ARG79 5.0 46.0 1.0 CZ C:PHE148 5.0 48.3 1.0

Arsenic binding site 4 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19)


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)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19) within 5.0Å range: probe atom residue distance (Å) B Occ D:As60 b:58.5 occ:1.00 AS D:CAS60 0.0 58.5 1.0 CE1 D:CAS60 2.0 60.7 1.0 CE2 D:CAS60 2.0 64.5 1.0 SG D:CAS60 2.3 47.6 1.0 CB D:CAS60 3.2 40.9 1.0 CA D:CAS60 3.4 37.7 1.0 N D:CAS60 4.0 36.1 1.0 O D:GLU59 4.3 36.2 1.0 CD2 D:LEU51 4.4 48.7 1.0 C D:GLU59 4.5 36.7 1.0 NE2 D:GLN49 4.6 45.8 1.0 C D:CAS60 4.6 35.8 1.0 CB D:LYS55 4.8 46.9 1.0 CG D:LYS55 4.8 49.4 1.0 O D:CAS60 4.9 35.4 1.0 CD D:GLN49 5.0 44.8 1.0

Arsenic binding site 5 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19)


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)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19) within 5.0Å range: probe atom residue distance (Å) B Occ D:As89 b:99.6 occ:1.00 AS D:CAS89 0.0 99.6 1.0 CE1 D:CAS89 2.0 0.7 1.0 CE2 D:CAS89 2.0 97.5 1.0 SG D:CAS89 2.2 90.1 1.0 CB D:CAS89 3.0 84.6 1.0 CA D:CAS89 3.5 76.0 1.0 O D:HOH209 3.5 61.1 1.0 C D:CAS89 4.1 69.9 1.0 N D:ILE90 4.2 67.7 1.0 O D:HOH211 4.6 71.0 1.0 OE2 D:GLU91 4.7 90.3 1.0 N D:CAS89 4.7 72.9 1.0 O D:LEU88 4.8 72.3 1.0

Arsenic binding site 6 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19)


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)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19) within 5.0Å range: probe atom residue distance (Å) B Occ F:As77 b:55.4 occ:1.00 AS F:CAS77 0.0 55.4 1.0 CE1 F:CAS77 2.0 55.8 1.0 CE2 F:CAS77 2.0 54.1 1.0 SG F:CAS77 2.2 41.0 1.0 CB F:CAS77 3.1 35.7 1.0 CA F:CAS77 3.7 31.1 1.0 CA F:GLY106 4.2 36.2 1.0 O F:THR105 4.3 32.6 1.0 N F:GLY106 4.4 34.8 1.0 C F:CAS77 4.4 30.5 1.0 C F:THR105 4.4 36.0 1.0 CE H:MET45 4.5 81.3 1.0 N F:ASN78 4.6 28.8 1.0 CE2 F:PHE148 4.7 57.5 1.0 CZ H:PHE109 4.7 57.0 1.0 CZ F:PHE148 4.8 58.3 1.0 NH2 F:ARG79 4.9 59.0 1.0 N F:CAS77 4.9 29.9 1.0

Arsenic binding site 7 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19)


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)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19) within 5.0Å range: probe atom residue distance (Å) B Occ G:As60 b:60.8 occ:1.00 AS G:CAS60 0.0 60.8 1.0 CE1 G:CAS60 2.0 61.0 1.0 CE2 G:CAS60 2.0 61.0 1.0 SG G:CAS60 2.3 53.0 1.0 CB G:CAS60 3.1 47.5 1.0 CA G:CAS60 3.4 45.6 1.0 N G:CAS60 4.1 44.8 1.0 CD2 G:LEU51 4.2 47.3 1.0 NE2 G:GLN49 4.4 45.8 1.0 O G:GLU59 4.6 48.7 1.0 C G:GLU59 4.6 47.3 1.0 C G:CAS60 4.6 44.7 1.0 CB G:LYS55 4.7 47.8 1.0 CG G:LYS55 4.8 49.3 1.0 CD G:GLN49 4.8 45.2 1.0 O G:CAS60 4.8 43.4 1.0

Arsenic binding site 8 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19)


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)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19) within 5.0Å range: probe atom residue distance (Å) B Occ G:As89 b:76.0 occ:1.00 AS G:CAS89 0.0 76.0 1.0 CE2 G:CAS89 2.0 72.7 1.0 CE1 G:CAS89 2.0 80.9 1.0 SG G:CAS89 2.2 57.6 1.0 CB G:CAS89 3.0 47.8 1.0 CA G:CAS89 3.6 43.6 1.0 O G:HOH212 3.8 48.9 1.0 N G:ILE90 4.1 38.7 1.0 C G:CAS89 4.1 39.7 1.0 O G:HOH211 4.3 37.7 1.0 O G:ILE90 4.6 38.2 1.0 C G:ILE90 4.7 38.4 1.0 N G:CAS89 4.9 42.0 1.0

Arsenic binding site 9 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19)


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)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19) within 5.0Å range: probe atom residue distance (Å) B Occ I:As77 b:48.1 occ:1.00 AS I:CAS77 0.0 48.1 1.0 CE2 I:CAS77 2.0 44.8 1.0 CE1 I:CAS77 2.0 49.5 1.0 SG I:CAS77 2.2 38.0 1.0 CB I:CAS77 3.1 32.0 1.0 CA I:CAS77 3.5 28.9 1.0 O I:HOH455 3.5 47.6 1.0 CA I:GLY106 4.0 30.9 1.0 O I:THR105 4.0 31.8 1.0 C I:CAS77 4.1 27.4 1.0 N I:GLY106 4.2 30.5 1.0 C I:THR105 4.2 32.9 1.0 N I:ASN78 4.2 27.1 1.0 N I:CAS77 4.8 27.1 1.0 O I:CAS77 4.9 27.1 1.0

Arsenic binding site 10 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19)


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)-3,3-Dimethyl-2-(Oxetane- 3-Carboxamido)Butanoyl)-4-Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl) Pyrrolidine-2-Carboxamide (Ligand 19) within 5.0Å range: probe atom residue distance (Å) B Occ J:As60 b:60.5 occ:1.00 AS J:CAS60 0.0 60.5 1.0 CE2 J:CAS60 2.0 63.6 1.0 CE1 J:CAS60 2.0 61.7 1.0 SG J:CAS60 2.3 43.8 1.0 CB J:CAS60 3.3 36.4 1.0 CA J:CAS60 3.5 35.3 1.0 CD2 J:LEU51 4.0 32.4 1.0 N J:CAS60 4.2 34.3 1.0 O J:GLU59 4.4 35.0 1.0 NE2 J:GLN49 4.5 41.3 1.0 C J:GLU59 4.6 35.5 1.0 CG J:LYS55 4.6 40.6 1.0 CB J:LYS55 4.7 37.6 1.0 C J:CAS60 4.7 34.0 1.0 O J:CAS60 5.0 31.6 1.0 CD J:GLN49 5.0 39.1 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