Fluorine in PDB 6nh6: Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine

The structure of Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine, PDB code: 6nh6 was solved by G.Chreifi, H.Li, T.L.Poulos, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	76.41 / 2.19
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	59.860, 152.820, 109.190, 90.00, 91.00, 90.00
R / Rfree (%)	19.6 / 24.7

The structure of Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine also contains other interesting chemical elements:

Zinc	(Zn)	2 atoms
Iron	(Fe)	4 atoms
Gadolinium	(Gd)	4 atoms
Chlorine	(Cl)	4 atoms

The binding sites of Fluorine atom in the Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine (pdb code 6nh6). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 8 binding sites of Fluorine where determined in the Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine, PDB code: 6nh6:
Jump to Fluorine binding site number: 1; 2; 3; 4; 5; 6; 7; 8;

Fluorine binding site 1 out of 8 in the Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ A:F503 b:53.3 occ:1.00 F12 A:KL7503 0.0 53.3 1.0 C12 A:KL7503 1.3 61.2 1.0 C11 A:KL7503 2.3 55.2 1.0 C13 A:KL7503 2.4 70.0 1.0 C06 A:KL7503 2.8 55.1 1.0 C09 A:KL7503 2.8 50.2 1.0 C05 A:KL7503 2.9 52.6 1.0 C1A A:HEM501 3.0 44.4 1.0 NA A:HEM501 3.1 42.4 1.0 N01 A:KL7503 3.2 53.2 1.0 C08 A:KL7503 3.3 52.7 1.0 CHA A:HEM501 3.3 41.8 1.0 C04 A:KL7503 3.4 45.4 1.0 ND A:HEM501 3.5 50.1 1.0 C2A A:HEM501 3.5 54.8 1.0 C4D A:HEM501 3.5 48.8 1.0 C4A A:HEM501 3.6 39.2 1.0 C16 A:KL7503 3.6 55.0 1.0 C02 A:KL7503 3.6 46.8 1.0 C14 A:KL7503 3.7 66.4 1.0 C03 A:KL7503 3.7 46.4 1.0 FE A:HEM501 3.7 42.3 1.0 C3A A:HEM501 3.8 43.4 1.0 C15 A:KL7503 4.1 62.1 1.0 CBA A:HEM501 4.2 77.0 1.0 C07 A:KL7503 4.3 47.9 1.0 CAA A:HEM501 4.4 66.6 1.0 CHB A:HEM501 4.4 40.1 1.0 NB A:HEM501 4.5 44.5 1.0 CGA A:HEM501 4.5 83.2 1.0 C1D A:HEM501 4.5 61.7 1.0 C3D A:HEM501 4.6 62.8 1.0 OE1 A:GLU361 4.6 51.5 1.0 N02 A:KL7503 4.6 41.1 1.0 CG2 A:VAL336 4.7 49.4 1.0 F16 A:KL7503 4.7 52.7 1.0 O2A A:HEM501 4.7 86.1 1.0 C1B A:HEM501 4.8 45.7 1.0 NC A:HEM501 4.8 53.0 1.0 O1A A:HEM501 4.9 85.5 1.0 CMA A:HEM501 5.0 41.2 1.0

Fluorine binding site 2 out of 8 in the Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ A:F503 b:52.7 occ:1.00 F16 A:KL7503 0.0 52.7 1.0 C16 A:KL7503 1.3 55.0 1.0 C11 A:KL7503 2.3 55.2 1.0 C15 A:KL7503 2.4 62.1 1.0 C09 A:KL7503 2.8 50.2 1.0 C17 A:KL7503 2.9 65.5 1.0 O A:HOH633 3.3 53.8 1.0 C19 A:KL7503 3.4 74.0 1.0 C08 A:KL7503 3.5 52.7 1.0 C12 A:KL7503 3.6 61.2 1.0 C14 A:KL7503 3.7 66.4 1.0 O2A A:HEM501 3.7 86.1 1.0 C18 A:KL7503 3.8 73.2 1.0 O A:HOH673 3.9 43.9 1.0 NE2 A:GLN247 4.1 65.5 1.0 C13 A:KL7503 4.1 70.0 1.0 CG2 A:VAL336 4.2 49.4 1.0 CGA A:HEM501 4.7 83.2 1.0 F12 A:KL7503 4.7 53.3 1.0 N20 A:KL7503 4.8 72.3 1.0 C06 A:KL7503 4.8 55.1 1.0

Fluorine binding site 3 out of 8 in the Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ B:F503 b:53.7 occ:1.00 F12 B:KL7503 0.0 53.7 1.0 C12 B:KL7503 1.3 46.8 1.0 C11 B:KL7503 2.3 38.4 1.0 C13 B:KL7503 2.4 48.2 1.0 C09 B:KL7503 2.7 31.0 1.0 C06 B:KL7503 2.8 42.4 1.0 C1A B:HEM501 2.9 18.8 1.0 C05 B:KL7503 3.0 38.4 1.0 NA B:HEM501 3.1 25.1 1.0 N01 B:KL7503 3.2 30.8 1.0 CHA B:HEM501 3.2 19.0 1.0 C08 B:KL7503 3.2 36.5 1.0 C4D B:HEM501 3.4 31.8 1.0 ND B:HEM501 3.4 23.3 1.0 C04 B:KL7503 3.5 26.1 1.0 C2A B:HEM501 3.6 38.9 1.0 C16 B:KL7503 3.6 43.1 1.0 C14 B:KL7503 3.6 52.7 1.0 C02 B:KL7503 3.7 32.5 1.0 C4A B:HEM501 3.7 23.7 1.0 FE B:HEM501 3.8 23.2 1.0 C03 B:KL7503 3.9 18.5 1.0 CBA B:HEM501 4.0 52.5 1.0 C3A B:HEM501 4.0 28.3 1.0 C15 B:KL7503 4.1 51.3 1.0 CAA B:HEM501 4.3 33.6 1.0 C3D B:HEM501 4.4 28.0 1.0 C1D B:HEM501 4.4 31.5 1.0 O2A B:HEM501 4.4 70.3 1.0 NB B:HEM501 4.5 25.2 1.0 C07 B:KL7503 4.5 18.4 1.0 CGA B:HEM501 4.6 76.0 1.0 CHB B:HEM501 4.6 17.8 1.0 N02 B:KL7503 4.6 22.7 1.0 OE1 B:GLU361 4.7 31.5 1.0 CG2 B:VAL336 4.7 24.7 1.0 F16 B:KL7503 4.7 40.4 1.0 NC B:HEM501 4.8 20.8 1.0 C2D B:HEM501 4.9 23.8 1.0 C1B B:HEM501 4.9 20.8 1.0

Fluorine binding site 4 out of 8 in the Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ B:F503 b:40.4 occ:1.00 F16 B:KL7503 0.0 40.4 1.0 C16 B:KL7503 1.3 43.1 1.0 C11 B:KL7503 2.4 38.4 1.0 C15 B:KL7503 2.4 51.3 1.0 O B:HOH772 2.5 50.1 1.0 C09 B:KL7503 2.8 31.0 1.0 C17 B:KL7503 2.9 49.6 1.0 O B:HOH616 3.1 47.0 1.0 C08 B:KL7503 3.5 36.5 1.0 C19 B:KL7503 3.6 52.6 1.0 C12 B:KL7503 3.6 46.8 1.0 O B:HOH687 3.6 38.4 1.0 C14 B:KL7503 3.6 52.7 1.0 C18 B:KL7503 3.8 56.3 1.0 O B:HOH709 4.1 46.6 1.0 C13 B:KL7503 4.1 48.2 1.0 CG2 B:VAL336 4.1 24.7 1.0 O2A B:HEM501 4.2 70.3 1.0 NE2 B:GLN247 4.2 28.6 1.0 CGA B:HEM501 4.6 76.0 1.0 F12 B:KL7503 4.7 53.7 1.0 O B:HOH642 4.8 37.4 1.0 C06 B:KL7503 4.8 42.4 1.0 N20 B:KL7503 4.9 50.3 1.0 C21 B:KL7503 4.9 42.9 1.0 O1A B:HEM501 5.0 88.2 1.0

Fluorine binding site 5 out of 8 in the Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 5 of Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ C:F503 b:62.5 occ:1.00 F12 C:KL7503 0.0 62.5 1.0 C12 C:KL7503 1.3 56.5 1.0 C11 C:KL7503 2.3 50.7 1.0 C13 C:KL7503 2.4 55.9 1.0 C09 C:KL7503 2.8 45.9 1.0 C05 C:KL7503 2.8 43.0 1.0 C06 C:KL7503 2.8 47.2 1.0 C08 C:KL7503 3.2 51.8 1.0 C1A C:HEM501 3.2 35.5 1.0 CHA C:HEM501 3.3 33.6 1.0 C4D C:HEM501 3.3 38.3 1.0 C04 C:KL7503 3.4 38.7 1.0 NA C:HEM501 3.4 35.6 1.0 N01 C:KL7503 3.4 45.9 1.0 ND C:HEM501 3.4 35.5 1.0 C16 C:KL7503 3.6 55.7 1.0 C14 C:KL7503 3.6 63.0 1.0 FE C:HEM501 3.9 31.9 1.0 C03 C:KL7503 3.9 34.1 1.0 C02 C:KL7503 3.9 41.0 1.0 C2A C:HEM501 4.0 49.4 1.0 C15 C:KL7503 4.1 60.1 1.0 C4A C:HEM501 4.1 36.4 1.0 C3D C:HEM501 4.1 44.7 1.0 C07 C:KL7503 4.2 38.3 1.0 C1D C:HEM501 4.2 44.5 1.0 CG2 C:VAL336 4.4 29.0 1.0 CBA C:HEM501 4.4 55.1 1.0 C3A C:HEM501 4.4 39.0 1.0 C2D C:HEM501 4.6 36.1 1.0 NB C:HEM501 4.6 30.1 1.0 CBD C:HEM501 4.6 59.0 1.0 CGA C:HEM501 4.7 73.0 1.0 F16 C:KL7503 4.7 55.8 1.0 NC C:HEM501 4.7 47.8 1.0 CAA C:HEM501 4.8 38.0 1.0 CE1 C:PHE353 4.9 38.7 1.0 OE1 C:GLU361 4.9 36.3 1.0 O1A C:HEM501 5.0 75.7 1.0 N02 C:KL7503 5.0 32.8 1.0 CHB C:HEM501 5.0 30.8 1.0

Fluorine binding site 6 out of 8 in the Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 6 of Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ C:F503 b:55.8 occ:1.00 F16 C:KL7503 0.0 55.8 1.0 C16 C:KL7503 1.3 55.7 1.0 C11 C:KL7503 2.4 50.7 1.0 C15 C:KL7503 2.4 60.1 1.0 O C:HOH602 2.8 51.4 1.0 C09 C:KL7503 2.8 45.9 1.0 C17 C:KL7503 2.9 58.9 1.0 C19 C:KL7503 3.2 66.4 1.0 C18 C:KL7503 3.6 66.0 1.0 C12 C:KL7503 3.6 56.5 1.0 C14 C:KL7503 3.6 63.0 1.0 C08 C:KL7503 3.7 51.8 1.0 O2A C:HEM501 3.7 79.9 1.0 C13 C:KL7503 4.1 55.9 1.0 NE2 C:GLN247 4.2 36.1 1.0 CG2 C:VAL336 4.4 29.0 1.0 CGA C:HEM501 4.5 73.0 1.0 N20 C:KL7503 4.6 61.6 1.0 F12 C:KL7503 4.7 62.5 1.0 O1A C:HEM501 4.9 75.7 1.0 C06 C:KL7503 5.0 47.2 1.0 C21 C:KL7503 5.0 66.5 1.0

Fluorine binding site 7 out of 8 in the Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 7 of Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ D:F503 b:57.9 occ:1.00 F12 D:KL7503 0.0 57.9 1.0 C12 D:KL7503 1.3 44.9 1.0 C11 D:KL7503 2.4 35.3 1.0 C13 D:KL7503 2.4 54.8 1.0 C09 D:KL7503 2.8 28.2 1.0 C1A D:HEM501 2.9 29.1 1.0 C06 D:KL7503 2.9 40.6 1.0 C05 D:KL7503 3.0 32.9 1.0 CHA D:HEM501 3.0 25.7 1.0 NA D:HEM501 3.1 27.4 1.0 C4D D:HEM501 3.2 26.9 1.0 ND D:HEM501 3.2 29.2 1.0 N01 D:KL7503 3.4 25.8 1.0 C08 D:KL7503 3.4 27.7 1.0 C04 D:KL7503 3.5 27.5 1.0 C16 D:KL7503 3.6 40.9 1.0 C2A D:HEM501 3.6 41.6 1.0 FE D:HEM501 3.6 25.5 1.0 C14 D:KL7503 3.6 50.9 1.0 C4A D:HEM501 3.8 22.4 1.0 C02 D:KL7503 3.8 26.7 1.0 C03 D:KL7503 3.9 22.2 1.0 C3A D:HEM501 4.1 37.2 1.0 C15 D:KL7503 4.1 54.9 1.0 CBA D:HEM501 4.1 66.7 1.0 C1D D:HEM501 4.2 31.9 1.0 C3D D:HEM501 4.2 34.9 1.0 C07 D:KL7503 4.3 23.0 1.0 CAA D:HEM501 4.5 48.4 1.0 NB D:HEM501 4.5 24.9 1.0 NC D:HEM501 4.6 22.1 1.0 C2D D:HEM501 4.6 23.9 1.0 CGA D:HEM501 4.6 74.7 1.0 O2A D:HEM501 4.7 72.9 1.0 F16 D:KL7503 4.7 37.9 1.0 CG2 D:VAL336 4.7 18.1 1.0 CHB D:HEM501 4.7 19.9 1.0 CBD D:HEM501 4.7 41.5 1.0 N02 D:KL7503 4.8 23.4 1.0 OE1 D:GLU361 5.0 27.8 1.0 C1B D:HEM501 5.0 27.6 1.0

Fluorine binding site 8 out of 8 in the Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 8 of Structure of the Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-(3-(Dimethylamino)Propyl)-2,6- Difluorophenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ D:F503 b:37.9 occ:1.00 F16 D:KL7503 0.0 37.9 1.0 C16 D:KL7503 1.3 40.9 1.0 C11 D:KL7503 2.3 35.3 1.0 C15 D:KL7503 2.4 54.9 1.0 C09 D:KL7503 2.8 28.2 1.0 C17 D:KL7503 2.9 51.2 1.0 O D:HOH602 3.1 65.7 1.0 O D:HOH717 3.3 43.0 1.0 O2A D:HEM501 3.4 72.9 1.0 C08 D:KL7503 3.4 27.7 1.0 O D:HOH782 3.4 45.7 1.0 C19 D:KL7503 3.6 62.5 1.0 C12 D:KL7503 3.6 44.9 1.0 C14 D:KL7503 3.6 50.9 1.0 C18 D:KL7503 3.7 53.8 1.0 NE2 D:GLN247 4.0 44.1 1.0 C13 D:KL7503 4.1 54.8 1.0 CG2 D:VAL336 4.3 18.1 1.0 O D:HOH625 4.3 31.3 1.0 CGA D:HEM501 4.5 74.7 1.0 C21 D:KL7503 4.5 56.8 1.0 N20 D:KL7503 4.6 56.4 1.0 C06 D:KL7503 4.7 40.6 1.0 F12 D:KL7503 4.7 57.9 1.0

H.T.Do, H.Li, G.Chreifi, T.L.Poulos, R.B.Silverman. Optimization of Blood-Brain Barrier Permeability with Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibitors Having A 2-Aminopyridine Scaffold. J. Med. Chem. V. 62 2690 2019.
ISSN: ISSN 1520-4804
PubMed: 30802056
DOI: 10.1021/ACS.JMEDCHEM.8B02032