Fluorine in PDB 6nhf: Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-4-Methylpyridin-2-Amine

The structure of Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-4-Methylpyridin-2-Amine, PDB code: 6nhf 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)	49.50 / 1.83
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	59.336, 152.557, 108.524, 90.00, 90.70, 90.00
R / Rfree (%)	18.3 / 21.9

The structure of Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-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 Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-4-Methylpyridin-2-Amine (pdb code 6nhf). 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 Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-4-Methylpyridin-2-Amine, PDB code: 6nhf:
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 Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-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 Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ A:F503 b:0.1 occ:1.00 F12 A:KNV503 0.0 0.1 1.0 C12 A:KNV503 1.3 0.7 1.0 C13 A:KNV503 2.3 0.4 1.0 C11 A:KNV503 2.4 96.5 1.0 F13 A:KNV503 2.7 0.9 1.0 C09 A:KNV503 2.9 83.4 1.0 C08 A:KNV503 2.9 79.9 1.0 CG2 A:VAL336 3.0 54.0 1.0 C05 A:KNV503 3.4 66.2 1.0 CBD A:HEM501 3.6 66.7 1.0 C14 A:KNV503 3.6 0.3 1.0 C06 A:KNV503 3.6 65.4 1.0 C16 A:KNV503 3.7 0.5 1.0 CB A:VAL336 4.0 52.5 1.0 C4D A:HEM501 4.0 45.5 1.0 C3D A:HEM501 4.1 55.2 1.0 C15 A:KNV503 4.1 0.8 1.0 CG1 A:VAL336 4.2 48.3 1.0 CHA A:HEM501 4.3 37.6 1.0 CE1 A:PHE353 4.4 49.2 1.0 ND A:HEM501 4.4 46.5 1.0 CAD A:HEM501 4.5 49.4 1.0 C2D A:HEM501 4.5 52.4 1.0 CZ A:PHE353 4.5 49.0 1.0 O2D A:HEM501 4.6 89.0 1.0 CGD A:HEM501 4.6 83.0 1.0 C1D A:HEM501 4.7 51.9 1.0 SD A:MET339 4.7 61.2 1.0 C04 A:KNV503 4.7 58.1 1.0 CBA A:HEM501 4.9 79.6 1.0 C1A A:HEM501 4.9 46.2 1.0 N01 A:KNV503 5.0 60.7 1.0

Fluorine binding site 2 out of 8 in the Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-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 Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ A:F503 b:0.9 occ:1.00 F13 A:KNV503 0.0 0.9 1.0 C13 A:KNV503 1.3 0.4 1.0 C14 A:KNV503 2.4 0.3 1.0 C12 A:KNV503 2.4 0.7 1.0 F12 A:KNV503 2.7 0.1 1.0 O2D A:HEM501 2.8 89.0 1.0 CBD A:HEM501 3.0 66.7 1.0 SD A:MET339 3.1 61.2 1.0 CGD A:HEM501 3.2 83.0 1.0 C15 A:KNV503 3.6 0.8 1.0 C11 A:KNV503 3.6 96.5 1.0 CG A:MET339 4.1 54.4 1.0 C16 A:KNV503 4.1 0.5 1.0 CE1 A:TYR475 4.2 52.1 1.0 CAD A:HEM501 4.2 49.4 1.0 CG1 A:VAL336 4.2 48.3 1.0 CE A:MET339 4.3 52.3 1.0 O1D A:HEM501 4.3 89.4 1.0 CG2 A:VAL336 4.4 54.0 1.0 C3D A:HEM501 4.6 55.2 1.0 OH A:TYR475 4.8 61.1 1.0 C17 A:KNV503 4.8 1.0 1.0 C09 A:KNV503 4.9 83.4 1.0 C18 A:KNV503 4.9 0.5 1.0 CB A:VAL336 4.9 52.5 1.0 CZ A:TYR475 5.0 60.1 1.0

Fluorine binding site 3 out of 8 in the Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-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 Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ B:F503 b:0.1 occ:1.00 F12 B:KNV503 0.0 0.1 1.0 C12 B:KNV503 1.3 0.7 1.0 C13 B:KNV503 2.3 0.1 1.0 C11 B:KNV503 2.4 0.7 1.0 F13 B:KNV503 2.7 0.3 1.0 CG2 B:VAL336 2.9 34.5 1.0 C08 B:KNV503 2.9 56.5 1.0 C09 B:KNV503 2.9 73.3 1.0 C05 B:KNV503 3.4 42.7 1.0 CBD B:HEM501 3.5 45.2 1.0 C14 B:KNV503 3.6 0.3 1.0 C06 B:KNV503 3.6 53.8 1.0 C16 B:KNV503 3.7 0.9 1.0 CB B:VAL336 3.8 26.3 1.0 CG1 B:VAL336 4.0 27.3 1.0 C4D B:HEM501 4.0 33.2 1.0 C3D B:HEM501 4.1 32.4 1.0 C15 B:KNV503 4.1 0.1 1.0 CHA B:HEM501 4.3 25.2 1.0 CE1 B:PHE353 4.3 28.1 1.0 CZ B:PHE353 4.4 32.6 1.0 CAD B:HEM501 4.4 36.2 1.0 ND B:HEM501 4.5 28.1 1.0 C2D B:HEM501 4.5 29.4 1.0 CGD B:HEM501 4.6 69.9 1.0 O2D B:HEM501 4.6 75.8 1.0 C1D B:HEM501 4.7 27.1 1.0 C04 B:KNV503 4.7 40.4 1.0 SD B:MET339 4.8 38.1 1.0 N01 B:KNV503 5.0 36.7 1.0 CBA B:HEM501 5.0 56.1 1.0 C1A B:HEM501 5.0 24.3 1.0

Fluorine binding site 4 out of 8 in the Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-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 Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ B:F503 b:0.3 occ:1.00 F13 B:KNV503 0.0 0.3 1.0 C13 B:KNV503 1.3 0.1 1.0 C14 B:KNV503 2.4 0.3 1.0 C12 B:KNV503 2.4 0.7 1.0 F12 B:KNV503 2.7 0.1 1.0 CBD B:HEM501 2.9 45.2 1.0 SD B:MET339 3.1 38.1 1.0 O2D B:HEM501 3.1 75.8 1.0 CGD B:HEM501 3.2 69.9 1.0 C15 B:KNV503 3.6 0.1 1.0 C11 B:KNV503 3.7 0.7 1.0 CG1 B:VAL336 4.0 27.3 1.0 CG B:MET339 4.0 34.4 1.0 CAD B:HEM501 4.1 36.2 1.0 O1D B:HEM501 4.1 72.7 1.0 C16 B:KNV503 4.1 0.9 1.0 CE1 B:TYR475 4.1 38.8 1.0 CE B:MET339 4.3 34.4 1.0 CG2 B:VAL336 4.4 34.5 1.0 O B:HOH728 4.5 46.0 1.0 C3D B:HEM501 4.6 32.4 1.0 CB B:VAL336 4.7 26.3 1.0 OH B:TYR475 4.8 53.4 1.0 C17 B:KNV503 4.8 0.5 1.0 C18 B:KNV503 4.9 0.7 1.0 C09 B:KNV503 4.9 73.3 1.0 CZ B:TYR475 4.9 52.9 1.0 CD1 B:TYR475 5.0 38.1 1.0

Fluorine binding site 5 out of 8 in the Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-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 Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ C:F503 b:0.2 occ:1.00 F12 C:KNV503 0.0 0.2 1.0 C12 C:KNV503 1.3 1.0 1.0 C13 C:KNV503 2.3 0.9 1.0 C11 C:KNV503 2.4 1.0 1.0 F13 C:KNV503 2.7 1.0 1.0 CG2 C:VAL336 2.9 50.3 1.0 C09 C:KNV503 2.9 88.2 1.0 C08 C:KNV503 2.9 77.6 1.0 CBD C:HEM501 3.5 62.0 1.0 C05 C:KNV503 3.5 67.6 1.0 C14 C:KNV503 3.6 0.4 1.0 C16 C:KNV503 3.6 0.4 1.0 C06 C:KNV503 3.7 67.5 1.0 CB C:VAL336 3.8 46.4 1.0 CG1 C:VAL336 3.8 42.7 1.0 C15 C:KNV503 4.1 0.6 1.0 C4D C:HEM501 4.3 44.1 1.0 C3D C:HEM501 4.3 43.1 1.0 CHA C:HEM501 4.5 32.5 1.0 O2D C:HEM501 4.5 85.0 1.0 CGD C:HEM501 4.5 79.5 1.0 CE1 C:PHE353 4.5 47.8 1.0 CZ C:PHE353 4.5 45.3 1.0 CAD C:HEM501 4.5 41.5 1.0 SD C:MET339 4.7 54.9 1.0 C2D C:HEM501 4.7 39.2 1.0 ND C:HEM501 4.7 41.3 1.0 C04 C:KNV503 4.8 59.2 1.0 C1D C:HEM501 5.0 43.7 1.0

Fluorine binding site 6 out of 8 in the Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-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 Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ C:F503 b:1.0 occ:1.00 F13 C:KNV503 0.0 1.0 1.0 C13 C:KNV503 1.3 0.9 1.0 C14 C:KNV503 2.3 0.4 1.0 C12 C:KNV503 2.4 1.0 1.0 F12 C:KNV503 2.7 0.2 1.0 CBD C:HEM501 3.1 62.0 1.0 O2D C:HEM501 3.1 85.0 1.0 SD C:MET339 3.1 54.9 1.0 CGD C:HEM501 3.3 79.5 1.0 C15 C:KNV503 3.6 0.6 1.0 C11 C:KNV503 3.6 1.0 1.0 CG C:MET339 3.9 49.2 1.0 CG1 C:VAL336 4.0 42.7 1.0 CE1 C:TYR475 4.0 60.0 1.0 C16 C:KNV503 4.1 0.4 1.0 O1D C:HEM501 4.2 87.7 1.0 CE C:MET339 4.3 41.6 1.0 CAD C:HEM501 4.4 41.5 1.0 CG2 C:VAL336 4.6 50.3 1.0 OH C:TYR475 4.7 76.5 1.0 C17 C:KNV503 4.8 0.8 1.0 CZ C:TYR475 4.8 65.0 1.0 C18 C:KNV503 4.8 0.1 1.0 CD1 C:TYR475 4.9 45.9 1.0 CB C:VAL336 4.9 46.4 1.0 C09 C:KNV503 4.9 88.2 1.0 C3D C:HEM501 4.9 43.1 1.0

Fluorine binding site 7 out of 8 in the Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-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 Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ D:F503 b:1.0 occ:1.00 F12 D:KNV503 0.0 1.0 1.0 C12 D:KNV503 1.3 0.6 1.0 C13 D:KNV503 2.3 0.4 1.0 C11 D:KNV503 2.4 99.0 1.0 F13 D:KNV503 2.7 0.6 1.0 CG2 D:VAL336 2.8 34.9 1.0 C09 D:KNV503 2.9 69.3 1.0 C08 D:KNV503 3.0 56.5 1.0 CBD D:HEM501 3.5 44.9 1.0 C05 D:KNV503 3.6 44.0 1.0 C14 D:KNV503 3.6 0.9 1.0 C16 D:KNV503 3.7 0.2 1.0 C06 D:KNV503 3.7 53.8 1.0 CB D:VAL336 4.0 28.1 1.0 C15 D:KNV503 4.1 0.8 1.0 CG1 D:VAL336 4.1 25.9 1.0 C4D D:HEM501 4.2 30.8 1.0 C3D D:HEM501 4.3 33.5 1.0 CHA D:HEM501 4.4 28.4 1.0 O2D D:HEM501 4.4 72.7 1.0 CGD D:HEM501 4.4 66.8 1.0 CAD D:HEM501 4.6 38.5 1.0 CE1 D:PHE353 4.6 26.5 1.0 CZ D:PHE353 4.7 32.2 1.0 ND D:HEM501 4.7 29.8 1.0 C2D D:HEM501 4.8 29.8 1.0 CBA D:HEM501 4.8 56.1 1.0 C04 D:KNV503 4.9 39.2 1.0 SD D:MET339 4.9 35.8 1.0 O D:HOH691 4.9 50.7 1.0 C1D D:HEM501 5.0 30.2 1.0

Fluorine binding site 8 out of 8 in the Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-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 Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with (S)-6-(2,3-Difluoro-5-(2-(1-Methylazetidin-2-Yl)Ethyl) Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ D:F503 b:0.6 occ:1.00 F13 D:KNV503 0.0 0.6 1.0 C13 D:KNV503 1.3 0.4 1.0 C14 D:KNV503 2.3 0.9 1.0 C12 D:KNV503 2.4 0.6 1.0 O2D D:HEM501 2.6 72.7 1.0 F12 D:KNV503 2.7 1.0 1.0 CBD D:HEM501 2.9 44.9 1.0 CGD D:HEM501 2.9 66.8 1.0 C15 D:KNV503 3.6 0.8 1.0 SD D:MET339 3.6 35.8 1.0 C11 D:KNV503 3.7 99.0 1.0 O1D D:HEM501 3.9 71.4 1.0 CE1 D:TYR475 4.0 36.4 1.0 C16 D:KNV503 4.1 0.2 1.0 CAD D:HEM501 4.3 38.5 1.0 CG1 D:VAL336 4.4 25.9 1.0 CG D:MET339 4.4 34.0 1.0 CG2 D:VAL336 4.6 34.9 1.0 O D:HOH691 4.6 50.7 1.0 C18 D:KNV503 4.7 0.7 1.0 OH D:TYR475 4.7 45.6 1.0 CE D:MET339 4.7 29.1 1.0 C17 D:KNV503 4.8 0.6 1.0 CZ D:TYR475 4.8 46.2 1.0 CD1 D:TYR475 4.9 34.1 1.0 C09 D:KNV503 4.9 69.3 1.0 C3D D:HEM501 4.9 33.5 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