Fluorine in PDB 6hdq: N-Terminal Bromodomain of Human BRD4 with : 8-(((1R,2R,3R,5S)-2-(2-(4, 4-Difluorocyclohexyl)Ethyl)-8-Azabicyclo[3.2.1]Octan-3-Yl)Amino)-3- Methyl-5-(5-Methylpyridin-3-Yl)-1,7-Naphthyridin-2(1H)-One

The structure of N-Terminal Bromodomain of Human BRD4 with : 8-(((1R,2R,3R,5S)-2-(2-(4, 4-Difluorocyclohexyl)Ethyl)-8-Azabicyclo[3.2.1]Octan-3-Yl)Amino)-3- Methyl-5-(5-Methylpyridin-3-Yl)-1,7-Naphthyridin-2(1H)-One, PDB code: 6hdq was solved by C.Chung, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	29.37 / 1.70
Space group	P 21 21 2
Cell size a, b, c (Å), α, β, γ (°)	40.360, 112.700, 30.420, 90.00, 90.00, 90.00
R / Rfree (%)	20.5 / 24.1

The binding sites of Fluorine atom in the N-Terminal Bromodomain of Human BRD4 with : 8-(((1R,2R,3R,5S)-2-(2-(4, 4-Difluorocyclohexyl)Ethyl)-8-Azabicyclo[3.2.1]Octan-3-Yl)Amino)-3- Methyl-5-(5-Methylpyridin-3-Yl)-1,7-Naphthyridin-2(1H)-One (pdb code 6hdq). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 2 binding sites of Fluorine where determined in the N-Terminal Bromodomain of Human BRD4 with : 8-(((1R,2R,3R,5S)-2-(2-(4, 4-Difluorocyclohexyl)Ethyl)-8-Azabicyclo[3.2.1]Octan-3-Yl)Amino)-3- Methyl-5-(5-Methylpyridin-3-Yl)-1,7-Naphthyridin-2(1H)-One, PDB code: 6hdq:
Jump to Fluorine binding site number: 1; 2;

Fluorine binding site 1 out of 2 in the N-Terminal Bromodomain of Human BRD4 with : 8-(((1R,2R,3R,5S)-2-(2-(4, 4-Difluorocyclohexyl)Ethyl)-8-Azabicyclo[3.2.1]Octan-3-Yl)Amino)-3- Methyl-5-(5-Methylpyridin-3-Yl)-1,7-Naphthyridin-2(1H)-One


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of N-Terminal Bromodomain of Human BRD4 with : 8-(((1R,2R,3R,5S)-2-(2-(4, 4-Difluorocyclohexyl)Ethyl)-8-Azabicyclo[3.2.1]Octan-3-Yl)Amino)-3- Methyl-5-(5-Methylpyridin-3-Yl)-1,7-Naphthyridin-2(1H)-One within 5.0Å range: probe atom residue distance (Å) B Occ A:F202 b:46.8 occ:1.00 F55 A:FZE202 0.0 46.8 1.0 C54 A:FZE202 1.4 41.9 1.0 F56 A:FZE202 2.2 43.5 1.0 C51 A:FZE202 2.3 39.8 1.0 C57 A:FZE202 2.3 41.5 1.0 CZ3 A:TRP81 2.8 30.0 0.3 CH2 A:TRP81 3.3 28.0 0.3 NE1 A:TRP81 3.3 33.9 0.3 C60 A:FZE202 3.7 40.8 1.0 C48 A:FZE202 3.7 40.6 1.0 CE3 A:TRP81 3.9 29.4 0.3 CE2 A:TRP81 4.1 33.5 0.3 C46 A:FZE202 4.2 39.5 1.0 CZ2 A:TRP81 4.2 33.8 0.3 CD1 A:TRP81 4.4 32.2 0.3 C01 A:FZE202 4.6 36.4 1.0 CZ2 A:TRP81 4.6 28.7 0.3

Fluorine binding site 2 out of 2 in the N-Terminal Bromodomain of Human BRD4 with : 8-(((1R,2R,3R,5S)-2-(2-(4, 4-Difluorocyclohexyl)Ethyl)-8-Azabicyclo[3.2.1]Octan-3-Yl)Amino)-3- Methyl-5-(5-Methylpyridin-3-Yl)-1,7-Naphthyridin-2(1H)-One


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of N-Terminal Bromodomain of Human BRD4 with : 8-(((1R,2R,3R,5S)-2-(2-(4, 4-Difluorocyclohexyl)Ethyl)-8-Azabicyclo[3.2.1]Octan-3-Yl)Amino)-3- Methyl-5-(5-Methylpyridin-3-Yl)-1,7-Naphthyridin-2(1H)-One within 5.0Å range: probe atom residue distance (Å) B Occ A:F202 b:43.5 occ:1.00 F56 A:FZE202 0.0 43.5 1.0 C54 A:FZE202 1.4 41.9 1.0 F55 A:FZE202 2.2 46.8 1.0 C51 A:FZE202 2.3 39.8 1.0 C57 A:FZE202 2.3 41.5 1.0 C60 A:FZE202 3.0 40.8 1.0 C48 A:FZE202 3.0 40.6 1.0 C12 A:FZE202 3.3 32.1 1.0 CZ3 A:TRP81 3.4 30.0 0.3 CG A:PRO82 3.5 28.4 1.0 C46 A:FZE202 3.6 39.5 1.0 C01 A:FZE202 3.6 36.4 1.0 NE1 A:TRP81 3.7 33.9 0.3 C05 A:FZE202 3.8 33.6 1.0 CE3 A:TRP81 4.0 29.4 0.3 CB A:PRO82 4.0 26.7 1.0 CD1 A:TRP81 4.2 32.2 0.3 C11 A:FZE202 4.3 30.9 1.0 CH2 A:TRP81 4.3 28.0 0.3 C14 A:FZE202 4.5 30.0 1.0 C15 A:FZE202 4.6 33.4 1.0 CE2 A:TRP81 4.7 33.5 0.3 CD A:PRO82 4.7 25.0 1.0 C43 A:FZE202 4.8 38.9 1.0 CD1 A:ILE146 4.8 33.7 1.0 CA A:PRO82 4.9 24.9 1.0

P.Bamborough, C.W.Chung, R.C.Furze, P.Grandi, A.M.Michon, R.J.Watson, D.J.Mitchell, H.Barnett, R.K.Prinjha, C.Rau, R.J.Sheppard, T.Werner, E.H.Demont. Aiming to Miss A Moving Target: Bromo and Extra Terminal Domain (Bet) Selectivity in Constrained ATAD2 Inhibitors. J. Med. Chem. V. 61 8321 2018.
ISSN: ISSN 1520-4804
PubMed: 30226378
DOI: 10.1021/ACS.JMEDCHEM.8B00862