Fluorine in PDB 5t92: Estrogen Receptor Alpha Ligand Binding Domain in Complex with (2E)-3- {4-[(1R)-2-(4-Fluorophenyl)-6-Hydroxy-1-Methy L-1,2,3,4- Tetrahydroisoquinolin-1-Yl]Phenyl}Prop-2-Enoic Acid

The structure of Estrogen Receptor Alpha Ligand Binding Domain in Complex with (2E)-3- {4-[(1R)-2-(4-Fluorophenyl)-6-Hydroxy-1-Methy L-1,2,3,4- Tetrahydroisoquinolin-1-Yl]Phenyl}Prop-2-Enoic Acid, PDB code: 5t92 was solved by C.Kirby, J.Baird, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	52.06 / 2.22
Space group	C 1 2 1
Cell size a, b, c (Å), α, β, γ (°)	105.220, 53.890, 97.110, 90.00, 114.11, 90.00
R / Rfree (%)	24 / 28.2

The binding sites of Fluorine atom in the Estrogen Receptor Alpha Ligand Binding Domain in Complex with (2E)-3- {4-[(1R)-2-(4-Fluorophenyl)-6-Hydroxy-1-Methy L-1,2,3,4- Tetrahydroisoquinolin-1-Yl]Phenyl}Prop-2-Enoic Acid (pdb code 5t92). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 2 binding sites of Fluorine where determined in the Estrogen Receptor Alpha Ligand Binding Domain in Complex with (2E)-3- {4-[(1R)-2-(4-Fluorophenyl)-6-Hydroxy-1-Methy L-1,2,3,4- Tetrahydroisoquinolin-1-Yl]Phenyl}Prop-2-Enoic Acid, PDB code: 5t92:
Jump to Fluorine binding site number: 1; 2;

Fluorine binding site 1 out of 2 in the Estrogen Receptor Alpha Ligand Binding Domain in Complex with (2E)-3- {4-[(1R)-2-(4-Fluorophenyl)-6-Hydroxy-1-Methy L-1,2,3,4- Tetrahydroisoquinolin-1-Yl]Phenyl}Prop-2-Enoic Acid


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Estrogen Receptor Alpha Ligand Binding Domain in Complex with (2E)-3- {4-[(1R)-2-(4-Fluorophenyl)-6-Hydroxy-1-Methy L-1,2,3,4- Tetrahydroisoquinolin-1-Yl]Phenyl}Prop-2-Enoic Acid within 5.0Å range: probe atom residue distance (Å) B Occ A:F601 b:41.4 occ:1.00 F27 A:77W601 0.0 41.4 1.0 C17 A:77W601 1.3 39.7 1.0 C16 A:77W601 2.4 39.8 1.0 C18 A:77W601 2.4 39.3 1.0 CD1 A:ILE424 3.1 64.2 1.0 ND1 A:HIS524 3.3 59.8 1.0 CG A:MET421 3.4 74.3 1.0 CB A:HIS524 3.5 53.1 1.0 C15 A:77W601 3.6 38.0 1.0 CG A:HIS524 3.6 57.4 1.0 C19 A:77W601 3.7 39.2 1.0 CA A:GLY521 3.7 37.2 1.0 SD A:MET421 3.7 78.7 1.0 O A:GLY521 3.8 37.9 1.0 C14 A:77W601 4.1 39.5 1.0 C A:GLY521 4.3 39.3 1.0 CE1 A:HIS524 4.3 59.6 1.0 CG1 A:ILE424 4.4 54.6 1.0 CE A:MET421 4.6 75.5 1.0 CD2 A:HIS524 4.7 59.9 1.0 CB A:ILE424 4.7 54.2 1.0 CA A:HIS524 4.8 51.4 1.0 N A:GLY521 4.8 37.7 1.0 CB A:MET421 4.8 70.5 1.0 O A:LYS520 4.8 45.0 1.0 CG2 A:ILE424 4.9 54.3 1.0 CG A:LEU525 5.0 61.6 1.0 N A:LEU525 5.0 49.7 1.0

Fluorine binding site 2 out of 2 in the Estrogen Receptor Alpha Ligand Binding Domain in Complex with (2E)-3- {4-[(1R)-2-(4-Fluorophenyl)-6-Hydroxy-1-Methy L-1,2,3,4- Tetrahydroisoquinolin-1-Yl]Phenyl}Prop-2-Enoic Acid


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Estrogen Receptor Alpha Ligand Binding Domain in Complex with (2E)-3- {4-[(1R)-2-(4-Fluorophenyl)-6-Hydroxy-1-Methy L-1,2,3,4- Tetrahydroisoquinolin-1-Yl]Phenyl}Prop-2-Enoic Acid within 5.0Å range: probe atom residue distance (Å) B Occ B:F601 b:43.0 occ:1.00 F27 B:77W601 0.0 43.0 1.0 C17 B:77W601 1.3 41.0 1.0 C16 B:77W601 2.3 38.8 1.0 C18 B:77W601 2.4 42.6 1.0 CB B:HIS524 3.2 57.6 1.0 CD1 B:ILE424 3.3 52.1 1.0 CA B:GLY521 3.5 40.3 1.0 CG B:MET421 3.6 71.0 1.0 O B:GLY521 3.6 44.2 1.0 C15 B:77W601 3.6 36.5 1.0 ND1 B:HIS524 3.6 63.9 1.0 CG B:HIS524 3.6 61.6 1.0 C19 B:77W601 3.6 41.3 1.0 SD B:MET421 4.0 76.4 1.0 C B:GLY521 4.0 44.7 1.0 C14 B:77W601 4.1 38.9 1.0 N B:GLY521 4.5 41.2 1.0 CE B:MET421 4.5 72.8 1.0 CA B:HIS524 4.6 56.4 1.0 O B:LYS520 4.6 44.1 1.0 CG1 B:ILE424 4.6 50.3 1.0 CE1 B:HIS524 4.6 63.3 1.0 CD2 B:HIS524 4.7 63.7 1.0 C B:LYS520 4.9 43.5 1.0 CB B:ILE424 5.0 51.2 1.0 N B:LEU525 5.0 58.2 1.0 N B:HIS524 5.0 55.2 1.0 CB B:MET421 5.0 66.3 1.0

H.E.Burks, T.Abrams, C.A.Kirby, J.Baird, A.Fekete, L.G.Hamann, S.Kim, F.Lombardo, A.Loo, D.Lubicka, K.Macchi, D.P.Mcdonnell, Y.Mishina, J.D.Norris, J.Nunez, C.Saran, Y.Sun, N.M.Thomsen, C.Wang, J.Wang, S.Peukert. Discovery of An Acrylic Acid Based Tetrahydroisoquinoline As An Orally Bioavailable Selective Estrogen Receptor Degrader For Er Alpha + Breast Cancer. J. Med. Chem. V. 60 2790 2017.
ISSN: ISSN 1520-4804
PubMed: 28296398
DOI: 10.1021/ACS.JMEDCHEM.6B01468