Arsenic in PDB 5nw1: Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18)

The structure of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18), PDB code: 5nw1 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)	49.50 / 2.10
Space group	P 41 2 2
Cell size a, b, c (Å), α, β, γ (°)	94.591, 94.591, 368.091, 90.00, 90.00, 90.00
R / Rfree (%)	19.6 / 23.8

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- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18) (pdb code 5nw1). 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- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18), PDB code: 5nw1:
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- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18)


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- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18) within 5.0Å range: probe atom residue distance (Å) B Occ A:As60 b:57.3 occ:1.00 AS A:CAS60 0.0 57.3 1.0 CE1 A:CAS60 2.0 58.7 1.0 CE2 A:CAS60 2.0 57.6 1.0 SG A:CAS60 2.3 39.7 1.0 CB A:CAS60 3.2 32.5 1.0 CA A:CAS60 3.5 31.5 1.0 CD2 A:LEU51 3.7 34.8 1.0 N A:CAS60 4.2 29.0 1.0 O A:GLU59 4.5 29.6 1.0 CG A:LYS55 4.6 35.1 1.0 CB A:LYS55 4.6 31.9 1.0 C A:GLU59 4.7 30.2 1.0 NE2 A:GLN49 4.7 48.2 1.0 C A:CAS60 4.7 31.8 1.0 O A:CAS60 4.9 31.6 1.0 CG A:LEU51 5.0 35.1 1.0 CD A:GLN49 5.0 45.9 1.0 CA A:LEU51 5.0 37.7 1.0

Arsenic binding site 2 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18)


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- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18) within 5.0Å range: probe atom residue distance (Å) B Occ A:As89 b:65.9 occ:1.00 AS A:CAS89 0.0 65.9 1.0 CE1 A:CAS89 2.0 69.1 1.0 CE2 A:CAS89 2.0 64.1 1.0 SG A:CAS89 2.2 58.3 1.0 CB A:CAS89 2.9 52.4 1.0 CA A:CAS89 3.4 48.7 1.0 C A:CAS89 4.0 44.0 1.0 N A:ILE90 4.1 43.8 1.0 OE2 A:GLU91 4.5 67.6 1.0 O A:HOH300 4.7 58.1 1.0 O A:ILE90 4.7 45.2 1.0 N A:CAS89 4.8 48.5 1.0 C A:ILE90 4.8 44.1 1.0 O A:CAS89 4.9 41.4 1.0 O A:LEU88 4.9 49.9 1.0

Arsenic binding site 3 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18)


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- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18) within 5.0Å range: probe atom residue distance (Å) B Occ C:As77 b:57.0 occ:1.00 AS C:CAS77 0.0 57.0 1.0 CE1 C:CAS77 2.0 55.6 1.0 CE2 C:CAS77 2.0 57.8 1.0 SG C:CAS77 2.2 41.1 1.0 CB C:CAS77 3.1 35.4 1.0 CA C:CAS77 3.6 30.6 1.0 CA C:GLY106 4.1 34.3 1.0 O C:THR105 4.2 33.8 1.0 N C:GLY106 4.4 33.0 1.0 C C:CAS77 4.4 30.2 1.0 C C:THR105 4.4 34.7 1.0 N C:ASN78 4.6 29.3 1.0 CZ K:PHE109 4.6 36.0 1.0 CE2 C:PHE148 4.6 55.8 1.0 O C:HOH410 4.7 52.0 1.0 CE K:MET45 4.8 79.1 1.0 N C:CAS77 4.8 28.7 1.0 O C:PHE76 4.9 29.3 1.0 CG2 C:ILE75 5.0 32.4 1.0

Arsenic binding site 4 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18)


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- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18) within 5.0Å range: probe atom residue distance (Å) B Occ D:As60 b:55.1 occ:1.00 AS D:CAS60 0.0 55.1 1.0 CE1 D:CAS60 2.0 59.5 1.0 CE2 D:CAS60 2.0 62.3 1.0 SG D:CAS60 2.2 46.9 1.0 CB D:CAS60 3.2 38.7 1.0 CA D:CAS60 3.4 35.5 1.0 N D:CAS60 4.1 34.1 1.0 CD2 D:LEU51 4.3 44.3 1.0 NE2 D:GLN49 4.3 43.5 1.0 O D:GLU59 4.4 34.2 1.0 C D:GLU59 4.5 34.4 1.0 C D:CAS60 4.6 33.7 1.0 CG D:LYS55 4.7 50.3 1.0 CB D:LYS55 4.8 47.5 1.0 CD D:GLN49 4.9 42.7 1.0 O D:CAS60 4.9 32.8 1.0

Arsenic binding site 5 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18)


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- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18) within 5.0Å range: probe atom residue distance (Å) B Occ D:As89 b:98.5 occ:1.00 AS D:CAS89 0.0 98.5 1.0 CE1 D:CAS89 2.0 0.0 1.0 CE2 D:CAS89 2.0 99.3 1.0 SG D:CAS89 2.2 93.5 1.0 CB D:CAS89 3.0 83.1 1.0 CA D:CAS89 3.4 75.0 1.0 O D:HOH225 3.5 59.1 1.0 N D:ILE90 4.0 65.6 1.0 C D:CAS89 4.0 68.2 1.0 N D:CAS89 4.7 72.2 1.0 OE2 D:GLU91 4.8 86.2 1.0 O D:LEU88 4.8 73.5 1.0 C D:ILE90 4.9 62.7 1.0 O D:ILE90 4.9 63.0 1.0 O D:HOH218 4.9 72.9 1.0 O D:CAS89 4.9 65.2 1.0

Arsenic binding site 6 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18)


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- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18) within 5.0Å range: probe atom residue distance (Å) B Occ F:As77 b:56.6 occ:1.00 AS F:CAS77 0.0 56.6 1.0 CE1 F:CAS77 2.0 56.3 1.0 CE2 F:CAS77 2.0 55.0 1.0 SG F:CAS77 2.2 41.5 1.0 CB F:CAS77 3.1 36.4 1.0 CA F:CAS77 3.7 32.8 1.0 CA F:GLY106 4.1 35.8 1.0 O F:THR105 4.3 36.2 1.0 N F:GLY106 4.4 35.8 1.0 C F:CAS77 4.4 32.4 1.0 C F:THR105 4.5 38.7 1.0 CE H:MET45 4.6 77.2 1.0 CE2 F:PHE148 4.6 57.9 1.0 N F:ASN78 4.7 30.6 1.0 CZ H:PHE109 4.8 57.4 1.0 CZ F:PHE148 4.9 60.2 1.0 NH2 F:ARG79 4.9 57.2 1.0 N F:CAS77 4.9 31.6 1.0

Arsenic binding site 7 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18)


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- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18) within 5.0Å range: probe atom residue distance (Å) B Occ G:As60 b:57.0 occ:1.00 AS G:CAS60 0.0 57.0 1.0 CE1 G:CAS60 2.0 56.5 1.0 CE2 G:CAS60 2.0 58.8 1.0 SG G:CAS60 2.2 51.2 1.0 CB G:CAS60 3.1 46.5 1.0 CA G:CAS60 3.4 45.4 1.0 CD2 G:LEU51 4.0 45.9 1.0 N G:CAS60 4.1 44.7 1.0 NE2 G:GLN49 4.2 44.0 1.0 C G:CAS60 4.6 44.8 1.0 CB G:LYS55 4.6 51.0 1.0 C G:GLU59 4.6 45.6 1.0 O G:GLU59 4.7 45.8 1.0 CD G:GLN49 4.7 42.0 1.0 CG G:LYS55 4.7 52.7 1.0 O G:CAS60 4.8 44.1 1.0 OE1 G:GLN49 5.0 41.0 1.0

Arsenic binding site 8 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18)


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- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18) within 5.0Å range: probe atom residue distance (Å) B Occ G:As89 b:77.8 occ:1.00 AS G:CAS89 0.0 77.8 1.0 CE2 G:CAS89 2.0 77.4 1.0 CE1 G:CAS89 2.0 83.3 1.0 SG G:CAS89 2.2 67.2 1.0 CB G:CAS89 3.1 51.4 1.0 CA G:CAS89 3.6 46.5 1.0 N G:ILE90 4.0 41.2 1.0 C G:CAS89 4.1 42.3 1.0 O G:HOH239 4.4 43.6 1.0 O G:ILE90 4.6 37.8 1.0 C G:ILE90 4.8 39.7 1.0 N G:CAS89 4.9 44.5 1.0

Arsenic binding site 9 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18)


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- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18) within 5.0Å range: probe atom residue distance (Å) B Occ I:As77 b:51.2 occ:1.00 AS I:CAS77 0.0 51.2 1.0 CE1 I:CAS77 2.0 54.0 1.0 CE2 I:CAS77 2.0 49.7 1.0 SG I:CAS77 2.2 38.8 1.0 CB I:CAS77 3.1 32.2 1.0 CA I:CAS77 3.5 29.5 1.0 CA I:GLY106 3.9 33.6 1.0 N I:GLY106 4.1 32.9 1.0 O I:THR105 4.1 31.9 1.0 C I:THR105 4.2 34.7 1.0 C I:CAS77 4.2 27.4 1.0 N I:ASN78 4.3 27.7 1.0 N I:CAS77 4.8 27.2 1.0 O I:PHE76 5.0 28.9 1.0

Arsenic binding site 10 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18)


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- (Cyclobutanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 18) within 5.0Å range: probe atom residue distance (Å) B Occ J:As60 b:56.0 occ:1.00 AS J:CAS60 0.0 56.0 1.0 CE1 J:CAS60 2.0 57.4 1.0 CE2 J:CAS60 2.0 58.9 1.0 SG J:CAS60 2.3 44.3 1.0 CB J:CAS60 3.2 36.6 1.0 CA J:CAS60 3.5 34.4 1.0 CD2 J:LEU51 4.0 32.5 1.0 N J:CAS60 4.2 32.8 1.0 NE2 J:GLN49 4.4 38.0 1.0 O J:GLU59 4.5 33.6 1.0 C J:GLU59 4.6 33.9 1.0 CB J:LYS55 4.7 37.0 1.0 CG J:LYS55 4.7 40.5 1.0 C J:CAS60 4.7 32.6 1.0 CD J:GLN49 4.9 36.4 1.0 O J:CAS60 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