Chlorine in PDB 5aau: Optimization of A Novel Binding Motif to to (E)-3-(3,5- Difluoro-4-((1R,3R)-2-(2-Fluoro-2-Methylpropyl)-3-Methyl-2, 3,4,9-Tetrahydro-1H-Pyrido(3,4-B)Indol-1-Yl)Phenyl)Acrylic Acid (AZD9496), A Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist

The structure of Optimization of A Novel Binding Motif to to (E)-3-(3,5- Difluoro-4-((1R,3R)-2-(2-Fluoro-2-Methylpropyl)-3-Methyl-2, 3,4,9-Tetrahydro-1H-Pyrido(3,4-B)Indol-1-Yl)Phenyl)Acrylic Acid (AZD9496), A Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist, PDB code: 5aau was solved by R.A.Norman, R.H.Bradbury, C.De Almeida, D.M.Andrews, P.Ballard, D.Buttar, R.J.Callis, G.S.Currie, J.O.Curwen, C.D.Davies, C.De Savi, C.S.Donald, L.J.L.Feron, S.C.Glossop, B.R.Hayter, G.Karoutchi, S.G.Lamont, P.Macfaul, T.Moss, S.E.Pearson, A.A.Rabow, M.Tonge, G.E.Walker, H.M.Weir, Z.Wilson, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	25.70 / 1.90
Space group	C 1 2 1
Cell size a, b, c (Å), α, β, γ (°)	106.407, 51.396, 85.181, 90.00, 93.66, 90.00
R / Rfree (%)	17.293 / 22.591

The binding sites of Chlorine atom in the Optimization of A Novel Binding Motif to to (E)-3-(3,5- Difluoro-4-((1R,3R)-2-(2-Fluoro-2-Methylpropyl)-3-Methyl-2, 3,4,9-Tetrahydro-1H-Pyrido(3,4-B)Indol-1-Yl)Phenyl)Acrylic Acid (AZD9496), A Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist (pdb code 5aau). This binding sites where shown within 5.0 Angstroms radius around Chlorine atom.
In total 2 binding sites of Chlorine where determined in the Optimization of A Novel Binding Motif to to (E)-3-(3,5- Difluoro-4-((1R,3R)-2-(2-Fluoro-2-Methylpropyl)-3-Methyl-2, 3,4,9-Tetrahydro-1H-Pyrido(3,4-B)Indol-1-Yl)Phenyl)Acrylic Acid (AZD9496), A Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist, PDB code: 5aau:
Jump to Chlorine binding site number: 1; 2;

Chlorine binding site 1 out of 2 in the Optimization of A Novel Binding Motif to to (E)-3-(3,5- Difluoro-4-((1R,3R)-2-(2-Fluoro-2-Methylpropyl)-3-Methyl-2, 3,4,9-Tetrahydro-1H-Pyrido(3,4-B)Indol-1-Yl)Phenyl)Acrylic Acid (AZD9496), A Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 1 of Optimization of A Novel Binding Motif to to (E)-3-(3,5- Difluoro-4-((1R,3R)-2-(2-Fluoro-2-Methylpropyl)-3-Methyl-2, 3,4,9-Tetrahydro-1H-Pyrido(3,4-B)Indol-1-Yl)Phenyl)Acrylic Acid (AZD9496), A Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl1553 b:27.9 occ:1.00 CL A:XBR1553 0.0 27.9 1.0 C23 A:XBR1553 1.8 23.1 1.0 C24 A:XBR1553 2.7 21.8 1.0 C22 A:XBR1553 2.7 23.9 1.0 O A:VAL533 3.6 60.3 1.0 C25 A:XBR1553 3.9 21.6 1.0 C21 A:XBR1553 4.0 22.1 1.0 CD A:PRO535 4.1 35.1 1.0 CG2 A:THR347 4.2 30.8 1.0 CD1 A:LEU525 4.2 31.6 1.0 C A:VAL533 4.3 57.2 1.0 CA A:VAL534 4.3 45.6 1.0 CD2 A:LEU525 4.4 33.6 1.0 OG1 A:THR347 4.4 28.4 1.0 C20 A:XBR1553 4.5 22.7 1.0 CG1 A:VAL534 4.5 48.7 1.0 N A:VAL534 4.6 50.2 1.0 CB A:THR347 4.7 30.0 1.0 CA A:THR347 4.7 28.4 1.0 CB A:ALA350 4.8 23.6 1.0 CH2 A:TRP383 4.8 20.8 1.0 N A:VAL533 4.9 64.2 1.0 CG A:LEU525 4.9 31.5 1.0 CB A:VAL534 4.9 47.4 1.0

Chlorine binding site 2 out of 2 in the Optimization of A Novel Binding Motif to to (E)-3-(3,5- Difluoro-4-((1R,3R)-2-(2-Fluoro-2-Methylpropyl)-3-Methyl-2, 3,4,9-Tetrahydro-1H-Pyrido(3,4-B)Indol-1-Yl)Phenyl)Acrylic Acid (AZD9496), A Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 2 of Optimization of A Novel Binding Motif to to (E)-3-(3,5- Difluoro-4-((1R,3R)-2-(2-Fluoro-2-Methylpropyl)-3-Methyl-2, 3,4,9-Tetrahydro-1H-Pyrido(3,4-B)Indol-1-Yl)Phenyl)Acrylic Acid (AZD9496), A Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl1547 b:27.5 occ:1.00 CL B:XBR1547 0.0 27.5 1.0 C23 B:XBR1547 1.8 23.9 1.0 C24 B:XBR1547 2.7 23.0 1.0 C22 B:XBR1547 2.8 24.3 1.0 O B:VAL533 3.4 36.0 1.0 C B:VAL533 3.9 37.2 1.0 C25 B:XBR1547 4.0 22.9 1.0 C21 B:XBR1547 4.1 22.7 1.0 CG2 B:THR347 4.2 24.1 1.0 CD1 B:LEU525 4.3 27.9 1.0 CB B:VAL533 4.3 41.0 1.0 CH2 B:TRP383 4.4 23.9 1.0 N B:VAL534 4.5 34.9 1.0 CD2 B:LEU525 4.5 29.1 1.0 CA B:VAL533 4.6 35.8 1.0 C20 B:XBR1547 4.6 22.3 1.0 OG1 B:THR347 4.6 23.6 1.0 CA B:VAL534 4.6 33.3 1.0 CB B:ALA350 4.6 17.7 1.0 CA B:THR347 4.8 22.9 1.0 CB B:THR347 4.8 23.3 1.0 CZ3 B:TRP383 4.9 25.3 1.0 CG2 B:VAL534 5.0 35.4 1.0 CD B:PRO535 5.0 31.2 1.0

C.De Savi, R.H.Bradbury, A.A.Rabow, R.A.Norman, C.De Almeida, D.M.Andrews, P.Ballard, D.Buttar, R.Callis, G.S.Currie, C.Davies, C.Donald, L.Feron, B.R.Hayter, S.Hussain, G.Karoutchi, S.Lamont, P.A.Macfaul, T.A.Moss, S.Pearson, M.Tonge, G.Walker, H.Weir, Z.Wilson. Optimization of A Novel Binding Motif to (E)-3-(3,5- Difluoro-4-((1R,3R)-2-(2-Fluoro-2-Methylpropyl)-3-Methyl-2, 3,4,9-Tetrahydro-1H-Pyrido[3,4-B]Indol-1-Yl)Phenyl)Acrylic Acid (AZD9496), A Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist. J.Med.Chem. V. 58 8128 2015.
ISSN: ISSN 0022-2623
PubMed: 26407012
DOI: 10.1021/ACS.JMEDCHEM.5B00984