Arsenic in PDB 5nvz: Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16)

The structure of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16), PDB code: 5nvz 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)	49.55 / 2.70
Space group	P 41 2 2
Cell size a, b, c (Å), α, β, γ (°)	94.757, 94.757, 368.110, 90.00, 90.00, 90.00
R / Rfree (%)	21.1 / 27

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- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16) (pdb code 5nvz). 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- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16), PDB code: 5nvz:
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- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16)


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- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16) within 5.0Å range: probe atom residue distance (Å) B Occ A:As60 b:69.7 occ:1.00 AS A:CAS60 0.0 69.7 1.0 CE2 A:CAS60 2.0 65.6 1.0 CE1 A:CAS60 2.0 67.7 1.0 SG A:CAS60 2.3 54.8 1.0 CB A:CAS60 3.3 43.0 1.0 CA A:CAS60 3.5 40.2 1.0 CD2 A:LEU51 3.9 39.9 1.0 N A:CAS60 4.2 38.0 1.0 O A:GLU59 4.6 39.5 1.0 C A:GLU59 4.6 39.3 1.0 NE2 A:GLN49 4.7 41.3 1.0 CG A:LYS55 4.7 43.3 1.0 CB A:LYS55 4.7 39.9 1.0 C A:CAS60 4.7 37.9 1.0 O A:CAS60 4.9 38.6 1.0 CD A:GLN49 4.9 40.5 1.0 OE1 A:GLN49 4.9 41.4 1.0

Arsenic binding site 2 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16)


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- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16) within 5.0Å range: probe atom residue distance (Å) B Occ A:As89 b:78.0 occ:1.00 AS A:CAS89 0.0 78.0 1.0 CE2 A:CAS89 2.0 75.9 1.0 CE1 A:CAS89 2.0 77.6 1.0 SG A:CAS89 2.2 69.5 1.0 CB A:CAS89 3.0 62.7 1.0 CA A:CAS89 3.7 55.9 1.0 N A:ILE90 4.1 51.3 1.0 C A:CAS89 4.2 52.6 1.0 OE2 A:GLU91 4.5 64.7 1.0 O A:ILE90 4.9 47.2 1.0 C A:ILE90 4.9 47.2 1.0

Arsenic binding site 3 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16)


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- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16) within 5.0Å range: probe atom residue distance (Å) B Occ C:As77 b:75.5 occ:1.00 AS C:CAS77 0.0 75.5 1.0 CE1 C:CAS77 2.0 75.7 1.0 CE2 C:CAS77 2.0 76.6 1.0 SG C:CAS77 2.2 60.3 1.0 CB C:CAS77 3.1 51.5 1.0 CA C:CAS77 3.7 45.8 1.0 CE K:MET45 4.2 95.2 1.0 CA C:GLY106 4.3 42.9 1.0 O C:THR105 4.4 40.0 1.0 CZ C:PHE148 4.5 76.2 1.0 C C:CAS77 4.5 44.0 1.0 C C:THR105 4.6 42.3 1.0 N C:GLY106 4.6 43.1 1.0 N C:ASN78 4.7 41.5 1.0 SD K:MET45 4.8 90.5 1.0 CZ K:PHE109 4.8 49.9 1.0 CE2 C:PHE148 4.8 71.8 1.0 O C:PHE76 4.8 39.6 1.0 N C:CAS77 4.9 41.3 1.0 NH2 C:ARG79 5.0 65.2 1.0

Arsenic binding site 4 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16)


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- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16) within 5.0Å range: probe atom residue distance (Å) B Occ D:As60 b:57.9 occ:1.00 AS D:CAS60 0.0 57.9 1.0 CE1 D:CAS60 2.0 57.6 1.0 CE2 D:CAS60 2.0 62.9 1.0 SG D:CAS60 2.2 52.4 1.0 CB D:CAS60 3.2 45.1 1.0 CA D:CAS60 3.4 41.6 1.0 N D:CAS60 4.1 40.6 1.0 CD2 D:LEU51 4.2 46.4 1.0 O D:GLU59 4.6 39.1 1.0 C D:GLU59 4.6 40.2 1.0 C D:CAS60 4.6 40.1 1.0 NE2 D:GLN49 4.6 44.6 1.0 O D:CAS60 4.8 40.5 1.0 CG D:LYS55 4.8 58.1 1.0 CB D:LYS55 4.9 55.9 1.0 CD D:GLN49 4.9 44.7 1.0 OE1 D:GLN49 4.9 42.9 1.0

Arsenic binding site 5 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16)


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- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16) within 5.0Å range: probe atom residue distance (Å) B Occ D:As89 b:0.6 occ:1.00 AS D:CAS89 0.0 0.6 1.0 CE1 D:CAS89 2.0 0.1 1.0 CE2 D:CAS89 2.0 0.4 1.0 SG D:CAS89 2.2 0.7 1.0 CB D:CAS89 3.1 98.8 1.0 CA D:CAS89 3.8 86.8 1.0 OE2 D:GLU91 4.3 90.7 1.0 N D:ILE90 4.3 79.1 1.0 C D:CAS89 4.4 84.4 1.0 O D:HOH214 4.6 71.5 1.0 O D:ILE90 5.0 69.2 1.0

Arsenic binding site 6 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16)


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- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16) within 5.0Å range: probe atom residue distance (Å) B Occ F:As77 b:67.8 occ:1.00 AS F:CAS77 0.0 67.8 1.0 CE1 F:CAS77 2.0 67.6 1.0 CE2 F:CAS77 2.0 69.9 1.0 SG F:CAS77 2.2 56.6 1.0 CB F:CAS77 3.2 50.4 1.0 CA F:CAS77 3.7 46.0 1.0 CA F:GLY106 4.2 44.3 1.0 CE H:MET45 4.4 95.4 1.0 O F:THR105 4.4 41.5 1.0 C F:CAS77 4.4 44.9 1.0 N F:GLY106 4.5 45.4 1.0 C F:THR105 4.5 45.8 1.0 N F:ASN78 4.6 43.5 1.0 CZ F:PHE148 4.7 66.1 1.0 CE2 F:PHE148 4.8 64.3 1.0 N F:CAS77 5.0 43.7 1.0

Arsenic binding site 7 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16)


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- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16) within 5.0Å range: probe atom residue distance (Å) B Occ G:As60 b:65.3 occ:1.00 AS G:CAS60 0.0 65.3 1.0 CE1 G:CAS60 2.0 66.1 1.0 CE2 G:CAS60 2.0 65.9 1.0 SG G:CAS60 2.2 59.1 1.0 CB G:CAS60 3.2 55.1 1.0 CA G:CAS60 3.4 54.4 1.0 N G:CAS60 4.1 54.1 1.0 CD2 G:LEU51 4.2 56.5 1.0 NE2 G:GLN49 4.3 54.6 1.0 CD G:GLN49 4.6 53.7 1.0 C G:GLU59 4.6 56.1 1.0 C G:CAS60 4.7 53.9 1.0 CG G:LYS55 4.7 58.4 1.0 CB G:LYS55 4.7 57.2 1.0 O G:GLU59 4.7 56.1 1.0 OE1 G:GLN49 4.8 53.6 1.0 O G:CAS60 4.9 52.6 1.0

Arsenic binding site 8 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16)


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- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16) within 5.0Å range: probe atom residue distance (Å) B Occ G:As89 b:94.6 occ:1.00 AS G:CAS89 0.0 94.6 1.0 CE2 G:CAS89 2.0 90.0 1.0 CE1 G:CAS89 2.0 0.8 1.0 SG G:CAS89 2.2 74.3 1.0 CB G:CAS89 3.1 63.1 1.0 CA G:CAS89 3.7 56.0 1.0 O G:HOH205 3.9 54.4 1.0 N G:ILE90 4.1 49.7 1.0 C G:CAS89 4.2 52.0 1.0 C G:ILE90 4.8 48.1 1.0 O G:ILE90 5.0 48.1 1.0

Arsenic binding site 9 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16)


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- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16) within 5.0Å range: probe atom residue distance (Å) B Occ I:As77 b:61.1 occ:1.00 AS I:CAS77 0.0 61.1 1.0 CE1 I:CAS77 2.0 62.7 1.0 CE2 I:CAS77 2.0 60.7 1.0 SG I:CAS77 2.2 49.4 1.0 CB I:CAS77 3.1 42.5 1.0 CA I:CAS77 3.6 38.3 1.0 CA I:GLY106 4.0 35.5 1.0 O I:THR105 4.2 33.7 1.0 N I:GLY106 4.2 36.2 1.0 C I:CAS77 4.3 38.0 1.0 C I:THR105 4.3 37.0 1.0 N I:ASN78 4.4 38.6 1.0 CE2 I:PHE148 4.9 48.9 1.0 N I:CAS77 4.9 35.9 1.0

Arsenic binding site 10 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2-(1- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16)


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- Acetylcyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4- (4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 16) within 5.0Å range: probe atom residue distance (Å) B Occ J:As60 b:66.0 occ:1.00 AS J:CAS60 0.0 66.0 1.0 CE1 J:CAS60 2.0 66.0 1.0 CE2 J:CAS60 2.0 65.8 1.0 SG J:CAS60 2.3 57.4 1.0 CB J:CAS60 3.3 47.6 1.0 CA J:CAS60 3.5 45.0 1.0 CD2 J:LEU51 4.1 41.9 1.0 N J:CAS60 4.2 42.6 1.0 NE2 J:GLN49 4.5 43.3 1.0 O J:GLU59 4.6 46.1 1.0 O J:HOH232 4.7 50.8 1.0 C J:CAS60 4.7 42.6 1.0 C J:GLU59 4.7 45.9 1.0 CG J:LYS55 4.7 42.1 1.0 CB J:LYS55 4.8 39.8 1.0 O J:CAS60 4.8 40.5 1.0 CD J:GLN49 4.8 41.8 1.0 OE1 J:GLN49 4.9 41.4 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