Arsenic in PDB 4w9f: Pvhl:Elob:Eloc in Complex with (2S,4R)-1-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5)

The structure of Pvhl:Elob:Eloc in Complex with (2S,4R)-1-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5), PDB code: 4w9f was solved by I.Van Molle, S.Hewitt, C.Galdeano, M.S.Gadd, A.Ciulli, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	92.68 / 2.10
Space group	P 41 2 2
Cell size a, b, c (Å), α, β, γ (°)	92.680, 92.680, 364.020, 90.00, 90.00, 90.00
R / Rfree (%)	20.5 / 22.9

Pages:

>>> Page 1 <<< Page 2, Binding sites: 11 - 11;

Binding sites:

The binding sites of Arsenic atom in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5) (pdb code 4w9f). This binding sites where shown within 5.0 Angstroms radius around Arsenic atom.
In total 11 binding sites of Arsenic where determined in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5), PDB code: 4w9f:
Jump to Arsenic binding site number: 1; 2; 3; 4; 5; 6; 7; 8; 9; 10;

Arsenic binding site 1 out of 11 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5)


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-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5) within 5.0Å range: probe atom residue distance (Å) B Occ A:As89 b:0.6 occ:0.99 AS A:CAS89 0.0 0.6 1.0 CE1 A:CAS89 2.0 99.4 1.0 CE2 A:CAS89 2.0 95.0 1.0 SG A:CAS89 2.2 87.1 1.0 CB A:CAS89 3.1 70.2 1.0 CA A:CAS89 3.8 57.4 1.0 C A:CAS89 3.9 59.1 1.0 N A:ILE90 4.2 44.6 1.0 C A:ILE90 4.7 40.5 1.0 O A:ILE90 4.8 42.3 1.0 O A:HOH239 4.8 43.1 1.0 N A:GLU91 4.9 41.3 1.0 O A:CAS89 4.9 55.0 1.0

Arsenic binding site 2 out of 11 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5)


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-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5) within 5.0Å range: probe atom residue distance (Å) B Occ B:As112 b:0.5 occ:1.00 AS B:CAS112 0.0 0.5 1.0 CE2 B:CAS112 2.0 95.2 1.0 CE1 B:CAS112 2.0 95.9 1.0 SG B:CAS112 2.2 79.1 1.0 CB B:CAS112 2.8 75.8 1.0 CE1 B:PHE77 3.7 45.1 1.0 CB B:SER39 3.9 49.9 1.0 CA B:CAS112 4.2 69.2 1.0 CB B:LEU110 4.3 40.2 1.0 CA B:SER39 4.4 49.6 1.0 CD1 B:PHE77 4.5 42.6 1.0 CZ B:PHE77 4.5 45.0 1.0 OG B:SER39 4.5 49.9 1.0 O B:LEU110 4.5 42.4 1.0 N B:CAS112 4.6 61.9 1.0 O B:ASP111 4.7 54.0 1.0 C B:ASP111 4.8 55.5 1.0 N B:SER39 4.8 53.2 1.0 C B:CAS112 4.8 63.0 1.0 OXT B:CAS112 4.9 66.0 1.0 CD1 B:LEU110 4.9 42.3 1.0 C B:LEU110 4.9 41.8 1.0 CD2 B:TYR76 4.9 32.1 1.0 CG1 B:VAL73 5.0 31.5 1.0

Arsenic binding site 3 out of 11 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5)


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-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5) within 5.0Å range: probe atom residue distance (Å) B Occ C:As77 b:62.7 occ:1.00 AS C:CAS77 0.0 62.7 1.0 CE2 C:CAS77 2.0 63.3 1.0 CE1 C:CAS77 2.0 63.6 1.0 SG C:CAS77 2.2 47.0 1.0 CB C:CAS77 3.1 40.9 1.0 CE K:MET45 3.6 77.8 1.0 CA C:CAS77 3.7 37.9 1.0 CZ C:PHE148 4.1 56.4 1.0 CA C:GLY106 4.4 51.1 1.0 O C:THR105 4.4 49.1 1.0 C C:CAS77 4.4 35.5 1.0 N C:GLY106 4.6 49.3 1.0 C C:THR105 4.6 51.6 1.0 N C:ASN78 4.6 34.9 1.0 CG K:MET45 4.7 67.5 1.0 CE2 C:PHE148 4.8 57.3 1.0 SD K:MET45 4.8 77.0 1.0 N C:CAS77 4.9 36.1 1.0 NE C:ARG79 5.0 69.7 1.0 CE1 C:PHE148 5.0 57.0 1.0

Arsenic binding site 4 out of 11 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5)


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-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5) within 5.0Å range: probe atom residue distance (Å) B Occ D:As89 b:0.5 occ:0.96 AS D:CAS89 0.0 0.5 1.0 CE1 D:CAS89 2.0 0.5 1.0 CE2 D:CAS89 2.0 0.2 1.0 SG D:CAS89 2.2 0.2 1.0 CB D:CAS89 3.1 81.1 1.0 CA D:CAS89 3.9 71.3 1.0 C D:CAS89 4.3 64.0 1.0 N D:ILE90 4.3 62.3 1.0 O D:HOH216 4.8 58.9 1.0 C D:ILE90 4.9 56.1 1.0 O D:ILE90 4.9 57.5 1.0 O D:CAS89 5.0 59.3 1.0

Arsenic binding site 5 out of 11 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5)


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-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5) within 5.0Å range: probe atom residue distance (Å) B Occ E:As112 b:0.8 occ:1.00 AS E:CAS112 0.0 0.8 1.0 CE2 E:CAS112 2.0 94.4 1.0 CE1 E:CAS112 2.0 97.2 1.0 SG E:CAS112 2.2 75.7 1.0 CB E:CAS112 2.8 68.0 1.0 CE1 E:PHE77 3.5 46.8 1.0 CD1 E:PHE77 4.2 44.0 1.0 CZ E:PHE77 4.3 43.8 1.0 CA E:CAS112 4.3 63.4 1.0 CB E:SER39 4.5 48.3 1.0 CD2 E:TYR76 4.5 30.3 1.0 CG1 E:VAL73 4.5 37.8 1.0 CB E:LEU110 4.5 44.5 1.0 CD2 F:LEU158 4.6 40.1 1.0 OXT E:CAS112 4.7 55.6 1.0 C E:CAS112 4.7 56.8 1.0 N E:CAS112 4.8 58.9 1.0 CE2 E:TYR76 4.8 31.4 1.0 OG1 E:THR38 4.9 60.2 1.0 OG E:SER39 5.0 46.0 1.0 CD1 E:LEU110 5.0 48.4 1.0

Arsenic binding site 6 out of 11 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5)


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-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5) within 5.0Å range: probe atom residue distance (Å) B Occ F:As77 b:58.0 occ:0.96 AS F:CAS77 0.0 58.0 1.0 CE2 F:CAS77 2.0 59.1 1.0 CE1 F:CAS77 2.0 58.8 1.0 SG F:CAS77 2.2 43.9 1.0 CB F:CAS77 3.1 37.5 1.0 CA F:CAS77 3.6 34.1 1.0 CE H:MET45 3.8 61.7 1.0 CA F:GLY106 4.0 47.1 1.0 N F:GLY106 4.3 46.3 1.0 CZ F:PHE148 4.3 51.4 1.0 O F:THR105 4.3 44.2 1.0 C F:THR105 4.4 48.5 1.0 C F:CAS77 4.4 33.0 1.0 CG H:MET45 4.6 58.8 1.0 N F:ASN78 4.7 32.5 1.0 NH2 F:ARG79 4.8 69.1 1.0 NE F:ARG79 4.8 60.7 1.0 SD H:MET45 4.8 61.3 1.0 N F:CAS77 4.9 34.0 1.0 CE1 F:PHE148 5.0 49.4 1.0

Arsenic binding site 7 out of 11 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5)


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-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5) within 5.0Å range: probe atom residue distance (Å) B Occ G:As89 b:0.9 occ:0.99 AS G:CAS89 0.0 0.9 1.0 CE1 G:CAS89 2.0 0.5 1.0 CE2 G:CAS89 2.0 97.4 1.0 SG G:CAS89 2.2 78.0 1.0 CB G:CAS89 3.1 59.7 1.0 N G:ILE90 3.5 44.8 1.0 CA G:CAS89 3.6 50.3 1.0 C G:CAS89 3.7 45.9 1.0 C G:ILE90 4.1 42.1 1.0 O G:HOH215 4.1 46.4 1.0 O G:ILE90 4.2 44.0 1.0 N G:GLU91 4.3 40.9 1.0 CA G:ILE90 4.4 42.5 1.0 O G:CAS89 4.4 42.7 1.0 CG G:GLU91 4.7 51.0 1.0 CA G:GLU91 4.7 41.9 1.0 CD G:GLU91 4.8 54.1 1.0 OE2 G:GLU91 4.9 55.5 1.0

Arsenic binding site 8 out of 11 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5)


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-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5) within 5.0Å range: probe atom residue distance (Å) B Occ I:As77 b:58.5 occ:0.94 AS I:CAS77 0.0 58.5 0.9 CE2 I:CAS77 2.0 56.7 0.9 CE1 I:CAS77 2.0 57.1 0.9 SG I:CAS77 2.2 44.6 0.9 CB I:CAS77 3.1 39.5 0.9 CA I:CAS77 3.5 36.5 0.9 CA I:GLY106 3.8 40.1 1.0 N I:GLY106 4.0 40.0 1.0 O I:THR105 4.1 41.5 1.0 C I:CAS77 4.1 35.5 0.9 C I:THR105 4.1 42.2 1.0 N I:ASN78 4.3 35.4 1.0 N I:CAS77 4.7 35.9 0.9 NH2 I:ARG79 4.8 62.8 1.0 CE2 I:PHE148 4.9 57.5 1.0 O I:CAS77 4.9 34.9 0.9 O I:GLY104 4.9 46.7 1.0 O I:PHE76 5.0 37.3 1.0

Arsenic binding site 9 out of 11 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5)


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-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5) within 5.0Å range: probe atom residue distance (Å) B Occ J:As89 b:66.9 occ:0.88 AS J:CAS89 0.0 66.9 0.9 CE1 J:CAS89 2.0 67.0 0.9 CE2 J:CAS89 2.0 69.0 0.9 SG J:CAS89 2.2 49.2 0.9 CB J:CAS89 3.1 42.3 0.9 CA J:CAS89 3.7 37.8 0.9 O J:HOH259 3.7 53.7 1.0 N J:ILE90 4.1 34.0 1.0 C J:CAS89 4.2 35.3 0.9 O J:ILE90 4.6 34.8 1.0 O J:HOH233 4.6 45.4 1.0 C J:ILE90 4.8 34.1 1.0 OE2 J:GLU91 5.0 48.9 1.0

Arsenic binding site 10 out of 11 in the Pvhl:Elob:Eloc in Complex with (2S,4R)-1-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5)


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-(3,3-Dimethylbutanoyl)-4- Hydroxy-N-(4-(4-Methylthiazol-5-Yl)Benzyl)Pyrrolidine-2-Carboxamide (Ligand 5) within 5.0Å range: probe atom residue distance (Å) B Occ K:As112 b:0.8 occ:1.00 AS K:CAS112 0.0 0.8 1.0 CE1 K:CAS112 2.0 1.0 1.0 CE2 K:CAS112 2.0 0.3 1.0 SG K:CAS112 2.2 0.9 1.0 CB K:CAS112 3.1 90.1 1.0 CB L:THR157 3.2 41.4 1.0 N K:CAS112 3.3 77.2 1.0 N L:LEU158 3.5 36.1 1.0 N L:LYS159 3.6 35.7 1.0 OG1 L:THR157 3.8 43.7 1.0 C K:ASP111 3.8 82.8 1.0 CA K:CAS112 3.9 72.4 1.0 CA L:THR157 4.0 38.8 1.0 CB L:LYS159 4.0 40.9 1.0 C L:THR157 4.0 36.9 1.0 CG2 L:THR157 4.0 42.9 1.0 CA K:ASP111 4.1 78.8 1.0 CA L:LEU158 4.3 35.0 1.0 O K:LEU110 4.3 81.1 1.0 CA L:LYS159 4.4 37.8 1.0 CB L:LEU158 4.5 36.2 1.0 C L:LEU158 4.5 35.0 1.0 O K:ASP111 4.5 87.3 1.0 O K:ALA107 4.6 46.5 1.0 C K:CAS112 4.9 57.2 1.0 O L:THR157 5.0 33.7 1.0 C K:LEU110 5.0 75.8 1.0

C.Galdeano, M.S.Gadd, P.Soares, S.Scaffidi, I.Van Molle, I.Birced, S.Hewitt, D.M.Dias, A.Ciulli. Structure-Guided Design and Optimization of Small Molecules Targeting the Protein-Protein Interaction Between the Von Hippel-Lindau (Vhl) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (Hif) Alpha Subunit with in Vitro Nanomolar Affinities. J.Med.Chem. V. 57 8657 2014.
ISSN: ISSN 0022-2623
PubMed: 25166285
DOI: 10.1021/JM5011258