Arsenic in PDB 5nvw: Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6)

The structure of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6), PDB code: 5nvw was solved by M.S.Gadd, P.Soares, C.Galdeano, A.Ciulli, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	48.93 / 2.20
Space group	P 41 2 2
Cell size a, b, c (Å), α, β, γ (°)	93.226, 93.226, 365.081, 90.00, 90.00, 90.00
R / Rfree (%)	20.1 / 24.9

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- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6) (pdb code 5nvw). 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- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6), PDB code: 5nvw:
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- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6)


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- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6) within 5.0Å range: probe atom residue distance (Å) B Occ A:As60 b:49.1 occ:1.00 AS A:CAS60 0.0 49.1 1.0 CE1 A:CAS60 2.0 46.8 1.0 CE2 A:CAS60 2.0 47.3 1.0 SG A:CAS60 2.3 35.7 1.0 CB A:CAS60 3.2 29.0 1.0 CA A:CAS60 3.5 27.4 1.0 CD2 A:LEU51 3.6 32.5 1.0 N A:CAS60 4.2 25.7 1.0 CB A:LYS55 4.5 26.6 1.0 CG A:LYS55 4.5 29.2 1.0 NE2 A:GLN49 4.6 40.3 1.0 C A:CAS60 4.7 27.4 1.0 O A:GLU59 4.7 26.7 1.0 C A:GLU59 4.8 26.8 1.0 CA A:LEU51 4.8 33.0 1.0 CG A:LEU51 4.9 32.7 1.0 CD A:GLN49 4.9 38.2 1.0 O A:CAS60 4.9 28.6 1.0 CB A:LEU51 4.9 32.9 1.0

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


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- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6) within 5.0Å range: probe atom residue distance (Å) B Occ A:As89 b:58.1 occ:1.00 AS A:CAS89 0.0 58.1 1.0 CE1 A:CAS89 2.0 62.1 1.0 CE2 A:CAS89 2.0 57.3 1.0 SG A:CAS89 2.2 49.5 1.0 CB A:CAS89 3.0 44.2 1.0 CA A:CAS89 3.4 40.6 1.0 O A:HOH237 3.6 42.0 1.0 N A:ILE90 4.0 35.2 1.0 C A:CAS89 4.0 36.7 1.0 OE2 A:GLU91 4.6 55.4 1.0 O A:HOH296 4.7 38.2 1.0 O A:ILE90 4.7 36.0 1.0 N A:CAS89 4.7 39.8 1.0 C A:ILE90 4.8 34.8 1.0 O A:LEU88 4.8 41.4 1.0 O A:CAS89 5.0 35.5 1.0

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


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- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6) within 5.0Å range: probe atom residue distance (Å) B Occ C:As77 b:45.6 occ:1.00 AS C:CAS77 0.0 45.6 1.0 CE2 C:CAS77 2.0 47.3 1.0 CE1 C:CAS77 2.0 46.2 1.0 SG C:CAS77 2.2 35.7 1.0 CB C:CAS77 3.1 32.5 1.0 CA C:CAS77 3.5 28.6 1.0 CA C:GLY106 4.1 33.4 1.0 C C:CAS77 4.3 28.0 1.0 O C:THR105 4.3 32.6 1.0 N C:GLY106 4.3 34.0 1.0 CE K:MET45 4.4 74.1 1.0 CZ K:PHE109 4.4 33.1 1.0 CZ C:PHE148 4.4 47.4 1.0 N C:ASN78 4.5 27.7 1.0 C C:THR105 4.5 34.4 1.0 CE2 C:PHE148 4.5 46.8 1.0 N C:CAS77 4.7 25.7 1.0 O C:PHE76 4.8 23.8 1.0 NH2 C:ARG79 4.9 58.9 1.0 CG2 C:ILE75 4.9 29.5 1.0 SD K:MET45 4.9 76.7 1.0 O C:GLY104 4.9 43.8 1.0 CE1 K:PHE109 5.0 34.5 1.0

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


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- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6) within 5.0Å range: probe atom residue distance (Å) B Occ D:As60 b:48.7 occ:1.00 AS D:CAS60 0.0 48.7 1.0 CE1 D:CAS60 2.0 51.8 1.0 CE2 D:CAS60 2.0 54.1 1.0 SG D:CAS60 2.2 38.9 1.0 CB D:CAS60 3.1 32.6 1.0 CA D:CAS60 3.3 29.3 1.0 N D:CAS60 3.9 28.8 1.0 CD2 D:LEU51 4.3 38.7 1.0 O D:GLU59 4.4 29.9 1.0 C D:GLU59 4.4 29.7 1.0 NE2 D:GLN49 4.5 37.5 1.0 C D:CAS60 4.6 27.1 1.0 CG D:LYS55 4.7 41.4 1.0 CB D:LYS55 4.7 39.5 1.0 O D:CAS60 4.9 26.3 1.0 CD D:GLN49 5.0 36.9 1.0

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


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- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6) within 5.0Å range: probe atom residue distance (Å) B Occ D:As89 b:92.2 occ:1.00 AS D:CAS89 0.0 92.2 1.0 CE1 D:CAS89 2.0 99.3 1.0 CE2 D:CAS89 2.0 90.1 1.0 SG D:CAS89 2.2 78.8 1.0 CB D:CAS89 2.9 73.0 1.0 CA D:CAS89 3.4 65.1 1.0 O D:HOH210 3.6 42.4 1.0 C D:CAS89 4.1 58.8 1.0 N D:ILE90 4.1 56.0 1.0 O D:HOH245 4.2 43.6 1.0 N D:CAS89 4.7 62.9 1.0 O D:LEU88 4.8 64.4 1.0 O D:ILE90 5.0 53.5 1.0 C D:ILE90 5.0 53.0 1.0 O D:CAS89 5.0 56.4 1.0

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


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- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6) within 5.0Å range: probe atom residue distance (Å) B Occ F:As77 b:44.9 occ:1.00 AS F:CAS77 0.0 44.9 1.0 CE1 F:CAS77 2.0 46.6 1.0 CE2 F:CAS77 2.0 48.2 1.0 SG F:CAS77 2.2 34.9 1.0 CB F:CAS77 3.1 31.0 1.0 CA F:CAS77 3.6 27.1 1.0 CA F:GLY106 4.1 35.4 1.0 CE H:MET45 4.2 59.7 1.0 N F:GLY106 4.3 34.1 1.0 CZ F:PHE148 4.3 51.4 1.0 O F:THR105 4.3 31.4 1.0 C F:CAS77 4.4 26.8 1.0 C F:THR105 4.4 35.0 1.0 N F:ASN78 4.6 26.4 1.0 CE2 F:PHE148 4.7 52.7 1.0 CG H:MET45 4.8 60.4 1.0 N F:CAS77 4.9 26.5 1.0 SD H:MET45 5.0 62.0 1.0

Arsenic binding site 7 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6)


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- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6) within 5.0Å range: probe atom residue distance (Å) B Occ G:As60 b:50.8 occ:1.00 AS G:CAS60 0.0 50.8 1.0 CE1 G:CAS60 2.0 51.9 1.0 CE2 G:CAS60 2.0 52.2 1.0 SG G:CAS60 2.2 43.2 1.0 CB G:CAS60 3.1 39.4 1.0 CA G:CAS60 3.3 38.2 1.0 CD2 G:LEU51 3.8 36.3 1.0 N G:CAS60 4.0 37.2 1.0 NE2 G:GLN49 4.2 34.9 1.0 O G:GLU59 4.5 38.7 1.0 C G:GLU59 4.5 38.8 1.0 C G:CAS60 4.5 37.5 1.0 CB G:LYS55 4.7 40.5 1.0 CD G:GLN49 4.7 33.5 1.0 CG G:LYS55 4.7 41.0 1.0 O G:CAS60 4.8 37.7 1.0 OE1 G:GLN49 5.0 32.5 1.0

Arsenic binding site 8 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6)


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- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6) within 5.0Å range: probe atom residue distance (Å) B Occ G:As89 b:67.6 occ:1.00 AS G:CAS89 0.0 67.6 1.0 CE2 G:CAS89 2.0 66.2 1.0 CE1 G:CAS89 2.0 71.2 1.0 SG G:CAS89 2.2 47.8 1.0 CB G:CAS89 2.9 39.4 1.0 CA G:CAS89 3.4 35.0 1.0 O G:HOH232 3.4 38.3 1.0 N G:ILE90 4.0 29.7 1.0 C G:CAS89 4.0 30.9 1.0 O G:HOH224 4.3 26.1 1.0 O G:ILE90 4.7 30.8 1.0 C G:ILE90 4.8 29.7 1.0 N G:CAS89 4.8 34.2 1.0 O G:CAS89 4.9 29.1 1.0 O G:LEU88 5.0 35.5 1.0

Arsenic binding site 9 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6)


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- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6) within 5.0Å range: probe atom residue distance (Å) B Occ I:As77 b:38.5 occ:1.00 AS I:CAS77 0.0 38.5 1.0 CE2 I:CAS77 2.0 37.2 1.0 CE1 I:CAS77 2.0 39.8 1.0 SG I:CAS77 2.2 29.7 1.0 CB I:CAS77 3.1 26.6 1.0 CA I:CAS77 3.5 24.3 1.0 CA I:GLY106 3.8 25.2 1.0 O I:THR105 4.0 24.7 1.0 N I:GLY106 4.1 25.2 1.0 C I:THR105 4.1 26.1 1.0 C I:CAS77 4.1 23.4 1.0 N I:ASN78 4.2 23.2 1.0 N I:CAS77 4.8 23.8 1.0 O I:GLY104 4.9 30.3 1.0 CE2 I:PHE148 4.9 36.4 1.0 O I:CAS77 5.0 23.0 1.0 CA I:THR105 5.0 27.3 1.0

Arsenic binding site 10 out of 12 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-((S)-2- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6)


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- (Cyclopropanecarboxamido)-3,3-Dimethylbutanoyl)-4-Hydroxy-N-(4-(4- Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 6) within 5.0Å range: probe atom residue distance (Å) B Occ J:As60 b:49.4 occ:1.00 AS J:CAS60 0.0 49.4 1.0 CE1 J:CAS60 2.0 51.2 1.0 CE2 J:CAS60 2.0 55.1 1.0 SG J:CAS60 2.3 35.9 1.0 CB J:CAS60 3.2 29.9 1.0 CA J:CAS60 3.5 29.2 1.0 CD2 J:LEU51 3.8 27.4 1.0 N J:CAS60 4.2 28.9 1.0 NE2 J:GLN49 4.3 38.0 1.0 O J:GLU59 4.5 31.6 1.0 CG J:LYS55 4.6 32.8 1.0 CB J:LYS55 4.6 30.2 1.0 C J:GLU59 4.6 30.8 1.0 C J:CAS60 4.7 28.2 1.0 CD J:GLN49 4.9 35.4 1.0 O J:CAS60 5.0 26.7 1.0 CA J:LEU51 5.0 26.9 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