Iron in PDB 6nh5: Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-Fluoro-5-(2-((2R,4S)-4-Fluoro-1-Methylpyrrolidin-2- Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine

The structure of Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-Fluoro-5-(2-((2R,4S)-4-Fluoro-1-Methylpyrrolidin-2- Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine, PDB code: 6nh5 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)	88.71 / 1.96
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	59.528, 152.760, 108.980, 90.00, 90.76, 90.00
R / Rfree (%)	19.7 / 24.1

The structure of Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-Fluoro-5-(2-((2R,4S)-4-Fluoro-1-Methylpyrrolidin-2- Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine also contains other interesting chemical elements:

Fluorine	(F)	8 atoms
Zinc	(Zn)	4 atoms
Gadolinium	(Gd)	2 atoms
Chlorine	(Cl)	4 atoms

The binding sites of Iron atom in the Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-Fluoro-5-(2-((2R,4S)-4-Fluoro-1-Methylpyrrolidin-2- Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine (pdb code 6nh5). This binding sites where shown within 5.0 Angstroms radius around Iron atom.
In total 4 binding sites of Iron where determined in the Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-Fluoro-5-(2-((2R,4S)-4-Fluoro-1-Methylpyrrolidin-2- Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine, PDB code: 6nh5:
Jump to Iron binding site number: 1; 2; 3; 4;

Iron binding site 1 out of 4 in the Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-Fluoro-5-(2-((2R,4S)-4-Fluoro-1-Methylpyrrolidin-2- Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine


Mono view


Stereo pair view

A full contact list of Iron with other atoms in the Fe binding site number 1 of Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-Fluoro-5-(2-((2R,4S)-4-Fluoro-1-Methylpyrrolidin-2- Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ A:Fe501 b:45.3 occ:1.00 FE A:HEM501 0.0 45.3 1.0 ND A:HEM501 2.1 55.6 1.0 NA A:HEM501 2.1 47.8 1.0 NC A:HEM501 2.1 56.3 1.0 NB A:HEM501 2.1 51.6 1.0 SG A:CYS184 2.3 38.5 1.0 C1A A:HEM501 3.1 47.4 1.0 C1B A:HEM501 3.1 53.7 1.0 C4D A:HEM501 3.1 58.6 1.0 C4A A:HEM501 3.1 48.4 1.0 C1D A:HEM501 3.1 66.9 1.0 C4B A:HEM501 3.1 58.8 1.0 C1C A:HEM501 3.1 59.7 1.0 C4C A:HEM501 3.1 64.0 1.0 CB A:CYS184 3.4 39.0 1.0 CHA A:HEM501 3.4 50.4 1.0 CHB A:HEM501 3.4 47.4 1.0 CHC A:HEM501 3.4 57.2 1.0 CHD A:HEM501 3.5 65.3 1.0 C04 A:KLD503 4.0 49.0 1.0 C05 A:KLD503 4.1 68.4 1.0 CA A:CYS184 4.1 38.6 1.0 C2B A:HEM501 4.3 50.7 1.0 C03 A:KLD503 4.3 49.9 1.0 C3B A:HEM501 4.3 56.1 1.0 C2A A:HEM501 4.3 63.1 1.0 C3A A:HEM501 4.3 45.8 1.0 C3D A:HEM501 4.3 62.9 1.0 C2D A:HEM501 4.3 62.7 1.0 C2C A:HEM501 4.3 64.3 1.0 C3C A:HEM501 4.3 64.7 1.0 C06 A:KLD503 4.4 67.4 1.0 C07 A:KLD503 4.4 54.4 1.0 NE1 A:TRP178 4.5 48.0 1.0 C02 A:KLD503 4.6 44.9 1.0 N01 A:KLD503 4.6 59.9 1.0 C A:CYS184 4.9 37.0 1.0 N A:GLY186 4.9 36.6 1.0 N A:VAL185 5.0 32.5 1.0

Iron binding site 2 out of 4 in the Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-Fluoro-5-(2-((2R,4S)-4-Fluoro-1-Methylpyrrolidin-2- Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine


Mono view


Stereo pair view

A full contact list of Iron with other atoms in the Fe binding site number 2 of Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-Fluoro-5-(2-((2R,4S)-4-Fluoro-1-Methylpyrrolidin-2- Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ B:Fe501 b:28.5 occ:1.00 FE B:HEM501 0.0 28.5 1.0 ND B:HEM501 2.0 31.3 1.0 NA B:HEM501 2.1 27.4 1.0 NB B:HEM501 2.1 30.2 1.0 NC B:HEM501 2.2 24.9 1.0 SG B:CYS184 2.3 25.0 1.0 C1D B:HEM501 3.0 30.3 1.0 C4D B:HEM501 3.1 34.5 1.0 C4A B:HEM501 3.1 26.6 1.0 C1B B:HEM501 3.1 25.0 1.0 C1A B:HEM501 3.1 27.7 1.0 C4C B:HEM501 3.1 27.4 1.0 C4B B:HEM501 3.2 32.4 1.0 C1C B:HEM501 3.2 33.1 1.0 CHB B:HEM501 3.4 24.4 1.0 CB B:CYS184 3.4 24.6 1.0 CHD B:HEM501 3.4 23.9 1.0 CHA B:HEM501 3.5 28.8 1.0 CHC B:HEM501 3.5 25.9 1.0 CA B:CYS184 4.1 25.4 1.0 C04 B:KLD503 4.1 31.5 1.0 C05 B:KLD503 4.2 38.3 1.0 C2D B:HEM501 4.2 29.2 1.0 C3D B:HEM501 4.2 28.9 1.0 C03 B:KLD503 4.2 31.5 1.0 C2B B:HEM501 4.3 32.5 1.0 C3A B:HEM501 4.3 21.9 1.0 NE1 B:TRP178 4.3 27.6 1.0 C2A B:HEM501 4.3 31.2 1.0 C3B B:HEM501 4.4 30.0 1.0 C3C B:HEM501 4.4 33.3 1.0 C2C B:HEM501 4.4 27.9 1.0 C06 B:KLD503 4.4 43.8 1.0 C02 B:KLD503 4.5 32.1 1.0 C07 B:KLD503 4.6 27.6 1.0 N01 B:KLD503 4.6 38.3 1.0 N B:GLY186 4.8 37.7 1.0 C B:CYS184 4.8 25.4 1.0 N B:VAL185 4.9 26.2 1.0 CD1 B:TRP178 5.0 28.2 1.0

Iron binding site 3 out of 4 in the Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-Fluoro-5-(2-((2R,4S)-4-Fluoro-1-Methylpyrrolidin-2- Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine


Mono view


Stereo pair view

A full contact list of Iron with other atoms in the Fe binding site number 3 of Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-Fluoro-5-(2-((2R,4S)-4-Fluoro-1-Methylpyrrolidin-2- Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ C:Fe501 b:35.4 occ:1.00 FE C:HEM501 0.0 35.4 1.0 ND C:HEM501 2.1 35.5 1.0 NC C:HEM501 2.1 45.1 1.0 NA C:HEM501 2.1 44.9 1.0 NB C:HEM501 2.1 39.8 1.0 SG C:CYS184 2.3 34.2 1.0 C1A C:HEM501 3.1 40.1 1.0 C1C C:HEM501 3.1 45.2 1.0 C4D C:HEM501 3.1 45.8 1.0 C4B C:HEM501 3.1 50.0 1.0 C4A C:HEM501 3.1 41.5 1.0 C1B C:HEM501 3.1 45.8 1.0 C1D C:HEM501 3.1 36.8 1.0 C4C C:HEM501 3.1 38.3 1.0 CB C:CYS184 3.3 34.6 1.0 CHC C:HEM501 3.4 38.3 1.0 CHA C:HEM501 3.4 34.6 1.0 CHB C:HEM501 3.5 39.1 1.0 CHD C:HEM501 3.5 39.4 1.0 CA C:CYS184 4.0 37.8 1.0 C04 C:KLD503 4.2 46.9 1.0 C2A C:HEM501 4.3 55.9 1.0 C3A C:HEM501 4.3 40.4 1.0 C3B C:HEM501 4.3 42.4 1.0 C2B C:HEM501 4.3 36.1 1.0 C3D C:HEM501 4.3 38.3 1.0 C2C C:HEM501 4.3 50.6 1.0 C05 C:KLD503 4.3 54.3 1.0 C2D C:HEM501 4.3 38.4 1.0 C3C C:HEM501 4.3 41.1 1.0 C03 C:KLD503 4.4 47.7 1.0 NE1 C:TRP178 4.5 42.3 1.0 C06 C:KLD503 4.5 53.5 1.0 C02 C:KLD503 4.6 42.5 1.0 N01 C:KLD503 4.7 47.6 1.0 C07 C:KLD503 4.7 55.3 1.0 N C:GLY186 4.8 39.5 1.0 C C:CYS184 4.8 30.0 1.0 N C:VAL185 4.9 32.3 1.0

Iron binding site 4 out of 4 in the Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-Fluoro-5-(2-((2R,4S)-4-Fluoro-1-Methylpyrrolidin-2- Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine


Mono view


Stereo pair view

A full contact list of Iron with other atoms in the Fe binding site number 4 of Structure of Human Endothelial Nitric Oxide Synthase Heme Domain in Complex with 6-(3-Fluoro-5-(2-((2R,4S)-4-Fluoro-1-Methylpyrrolidin-2- Yl)Ethyl)Phenethyl)-4-Methylpyridin-2-Amine within 5.0Å range: probe atom residue distance (Å) B Occ D:Fe501 b:23.2 occ:1.00 FE D:HEM501 0.0 23.2 1.0 ND D:HEM501 2.1 36.4 1.0 NA D:HEM501 2.1 24.9 1.0 NB D:HEM501 2.1 29.9 1.0 NC D:HEM501 2.1 22.2 1.0 SG D:CYS184 2.3 23.4 1.0 C1D D:HEM501 3.1 33.4 1.0 C4A D:HEM501 3.1 24.9 1.0 C4D D:HEM501 3.1 33.5 1.0 C1A D:HEM501 3.1 27.7 1.0 C1B D:HEM501 3.1 31.0 1.0 C4C D:HEM501 3.1 22.5 1.0 C1C D:HEM501 3.2 25.1 1.0 C4B D:HEM501 3.2 24.7 1.0 CB D:CYS184 3.3 21.3 1.0 CHB D:HEM501 3.4 28.4 1.0 CHD D:HEM501 3.4 27.6 1.0 CHA D:HEM501 3.4 25.6 1.0 CHC D:HEM501 3.5 23.5 1.0 CA D:CYS184 4.1 20.1 1.0 C04 D:KLD502 4.1 28.1 1.0 C03 D:KLD502 4.2 26.9 1.0 C3D D:HEM501 4.3 33.4 1.0 C2D D:HEM501 4.3 32.5 1.0 C3A D:HEM501 4.3 32.9 1.0 C2A D:HEM501 4.3 32.9 1.0 C2B D:HEM501 4.3 35.9 1.0 C3B D:HEM501 4.4 30.0 1.0 C3C D:HEM501 4.4 30.0 1.0 C07 D:KLD502 4.4 23.9 1.0 C2C D:HEM501 4.4 26.7 1.0 NE1 D:TRP178 4.4 24.7 1.0 C05 D:KLD502 4.4 38.0 1.0 C02 D:KLD502 4.6 28.9 1.0 N D:GLY186 4.8 23.1 1.0 C D:CYS184 4.8 25.2 1.0 C06 D:KLD502 4.8 35.1 1.0 N01 D:KLD502 4.9 29.0 1.0 N D:VAL185 4.9 25.4 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